Bain, who publicly announced he had bowel cancer in 2015, revealed last month that his liver was failing and that he was retiring from reviewing games.
“I’m currently coming to terms with the fact that I don’t have long left,” he wrote in a lengthy post on Reddit.
He said his body had become resistant to all forms of chemotherapy and that his wife Genna would be taking over his YouTube channel.
Bain wrote: “I can’t do the job anymore. I’m under the influence of too much medication to think clearly.”
A message on his official Twitter account confirmed his passing, while his wife tweeted: “Rest in Peace my Dearest Love.”
“I’m more overwhelmed with grief than I could possibly express,” she wrote.
Tributes poured in for the popular YouTuber with fans describing Bain as a “warrior”, a “fighter” and “an inspiration”.
One tweeted: “One of the best game reviewers that was. Thanks for everything you’ve done John.”
Another wrote: “I never thought the death of a man I never met would affect me so much. I literally cannot put into words how much your channel and podcast affected me for the better. Rest now good sir. You will be truly missed.”