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Diane Simmons (née Seidelman) was Tom Tucker's co-anchor on Quahog 5 News and eventually became a murderer. Although when the series started, she and Tom seemed to have a healthy and at times possibly sexual relationship, that quickly changed to where they instead bicker a lot on the air, and she soon became the butt of his jokes. This relationship started spiraling around the time of her 40th birthday. She also hosted a talk show called Diane!, on which the Griffins were guests and exposed their secrets. The show was first seen in "Fifteen Minutes of Shame".
In "Patriot Games", it was revealed that she once had a husband, before he committed suicide, as commented once by Tom on the air, causing her to break down crying. She admits to being a bit of a bigot, such as once openly joking on the air that she is racist against black people, though she believed they were off the air since Peter Griffin had cut off Quahog's television signal. During the Special People's Games in "Ready, Willing, and Disabled" she and Tom commented together how watching the game would give them all a sick sort of laugh, and how all of them were most likely going to hell for it.
In "The King Is Dead", it was revealed that Diane's maiden name is "Seidelman". Simmons is also a dedicated actress having done some pretentious student films in college. At one point, she was set to play the role of Anna in The King and I having stolen the role from Loretta Brown, during Lois Griffin's first theatrical production. Unfortunately, Peter Griffin, who stole control of the show from Lois as producer, later changed the script so massively much that even Diane couldn't stand the direction the show was taking and quit. Peter took over the role personally, turning Anna from a British female school teacher, into a male, cybernetic assassin from the future.
In "And Then There Were Fewer", Diane reveals she has turned 40, and becomes the murderer of James Woods, Muriel Goldman, Derek Wilcox, Priscilla and Stephanie. She explains her plan to murder Woods and frame her co-anchor, Tom Tucker, to Lois, nearly murdering her as well. It was revealed that she dated Woods and Tom successfully convinced the network to replace her at the news desk, as well as Woods dumping Diane, which resulted in Diane to seek vengeance. However, before pulling the trigger, she is shot and killed by Stewie and falls off of a cliff to her death; Stewie then declares only he is allowed to kill Lois. In a message on his Twitter account, Seth MacFarlane confirmed that Diane and the other characters that were killed are dead.
- Stephanie - Set up a firearm to cook off and pointed it at the head seat at the table. Stephanie was an unintended victim, as the bullet was intended for James Woods, who was to sit at the head of the table.
- James Woods - Stabbed during a power outage in revenge for him dumping her although he was later resurrected shortly afterwards due to being a celebrity.
- Muriel Goldman - Stabbed for discovering that she is the murderer of Stephanie and James Woods.
- Derek Wilcox - Bludgeoned with James Woods' golden globe as he had attempted to summon first responders for help. Dr. Hartman declares that Derek was killed before he fell, and that his death was from a blunt object.
- Priscilla - Had her throat slit for seeing her with the knife and becoming hysterical. Her body was planted in a vent shaft in Tucker's room, along with the golden globe used to strike Derek, in an attempt to frame Tucker for the murders.
- Lois Griffin (attempted) - She attempts to kill Lois to keep anyone from finding out she had killed the previous victims, but just before she pulled the trigger, Stewie Griffin shot Diane with a sniper rifle, and she tumbled off a cliff into the ocean.
- FG101 "Death Has a Shadow"
- FG102 "I Never Met the Dead Man"
- FG107 "Brian: Portrait of a Dog"
- FG202 "Holy Crap"
- FG203 "Da Boom"
- FG204 "Brian in Love"
- FG205 "Love Thy Trophy"
- FG206 "Death Is a Bitch"
- FG207 "The King Is Dead"
- FG209 "If I'm Dyin', I'm Lyin'"
- FG210 "Running Mates"
- FG212 "Fifteen Minutes of Shame"
- FG214 "Let's Go to the Hop"
- FG215 "Dammit Janet!"
- FG218 "E. Peterbus Unum"
- FG220 "Wasted Talent"
- FG304 "One if by Clam, Two if by Sea"
- FG306 "Death Lives"
- FG307 "Lethal Weapons"
- FG308 "The Kiss Seen Around the World"
- FG309 "Mr. Saturday Knight"
- FG312 "To Love and Die in Dixie"
- FG315 "Ready, Willing, and Disabled"
- FG317 "Brian Wallows and Peter's Swallows"
- FG321 "Family Guy Viewer Mail No. 1"
- FG401 "North by North Quahog"
- FG402 "Fast Times at Buddy Cianci Jr. High"
- FG403 "Blind Ambition"
- FG404 "Don't Make Me Over"
- FG406 "Petarded" (on DVD only)
- FG409 "Breaking Out is Hard to Do"
- FG414 "PTV"
- FG416 "The Courtship of Stewie's Father"
- FG418 "The Father, the Son, and the Holy Fonz"
- FG420 "Patriot Games"
- FG423 "Deep Throats"
- FG425 "You May Now Kiss the...Uh...Guy Who Receives"
- FG426 "Petergeist"
- FG427 "Untitled Griffin Family History"
- FG428 "Stewie B. Goode"
- FG501 "Stewie Loves Lois"
- FG503 "Hell Comes to Quahog"
- FG506 "Prick Up Your Ears"
- FG508 "Barely Legal"
- FG515 "Boys Do Cry"
- FG606 "Padre de Familia"
- FG607 "Peter's Daughter"
- FG706 "Tales of a Third Grade Nothing"
- FG709 "The Juice Is Loose"
- FG711 "Not All Dogs Go To Heaven"
- FG712 "420"
- FG808 "Dog Gone"
- FG811 "Dial Meg for Murder"
- FG812 "Extra Large Medium"
- FG813 "Go, Stewie, Go!"
- FG816 "April in Quahog"
- FG901 "And Then There Were Fewer" (dies in this episode)
- FG902 "Excellence in Broadcasting" (mentioned)
- FG909 "And I'm Joyce Kinney" (mentioned)
- FG1013 "Tom Tucker: The Man and His Dream" (mentioned)