The actor declared that Reiser, who based 50/50 on his own cancer battle, deserves to hear his name called when the Oscar nominations are announced on January 24.
"I think Will, honestly, has the best shot of being nominated out of anyone with the movie," Rogen told Vulture.
Rogen recalled that his one major award nod was being nominated for his writing on Da Ali G Show, but the prize ultimately went to The Daily Show.
The comic joked about the likelihood of ever receiving an award, saying: "I feel like if I won an award and I was giving my speech and the music started, that's all I'd remember, the humiliation I felt when the music started. It would mar the entire experience for me."
Rogen will host the upcoming Independent Spirit Awards on February 25.
He has also apparently signed on to produce and potentially star in the Disney film The B Team.
> Seth Rogen hints at Pineapple Express 2
> Joseph Gordon-Levitt: 'Seth Rogen called me in dire straits for 50/50'
Watch Seth Rogen and Will Reiser discuss 50/50 with Digital Spy below: