Hoffman, who played a foul-mouthed former convict on the gritty HBO show, insisted executives made a "hasty decision" to cancel the series last year (12) following animal cruelty complaints in a recent interview.
The Tootsie star went on to claim that facts PETA officials served up to the media following the deaths of three horses connected to the TV drama were "so distorted".
And now one of PETA's Associate Director Michelle Cho is firing back, calling his remarks "cold and totally irresponsible".
In the letter, obtained by WENN, Cho writes, "God help us all if having three horses die during a TV series wasn't or - if you were oblivious then - isn't now enough for you to think that something might be wrong with the animal welfare safeguards for the production.
"How many dead animals on your TV show would it take to make you even slightly uncomfortable? Six? Twenty? All the horses?"
She adds, "You are one actor, but twelve whistleblowers who worked on Luck contacted PETA, and they all made the same allegations: The horses being used were unfit, arthritic, drugged, and pushed beyond their capabilities. There is nothing accidental about this."
Reminding the actor that PETA bosses asked for his help as the show's executive producer and star, she adds, "You ignored that overture and at least one other horse died just days later. That horse's blood is on your hands.
"As an executive producer, you most definitely shared responsibility for ensuring that every effort was being made to create a safe environment for the animals used, and you failed. The corpses of three horses are evidence that you and others in positions of authority shirked your duties.
"Now, to add insult to real-life injury, you have brazenly decided to defend that conduct and to take HBO to task for pulling the plug on this deadly show.
"While you have dismissed the deaths, the authorities haven't. The allegations remain under investigation by law enforcement, the California Horse Racing Board, and the California Veterinary Medical Association. It is clear to us, Mr. Hoffman, that you are a man without a heart or a conscience or the courage to apologize in any way for your role in the deaths and injuries that befell animals on the set of Luck. The bottom line is this: No animal should die for the fleeting entertainment of a TV show."
And Cho concludes her angry letter by suggesting Hoffman is "out of touch with a world that cares about animals".