Irfan has been replaced by Kerala medium-pacer Sandeep Warrier in the India Red squad to be led by his brother Yusuf Pathan.
"Irfan Pathan has been ruled out of the NKP Salve Challenger Trophy, due to injury," BCCI secretary Sanjay Patel said in a statement.
"The All-India Senior Selection Committee has replaced him with Sandeep Warrier in the India Red squad," he added.
Irfan, who has been regularly troubled by injuries since playing a crucial role in India's ODI series win in Sri Lanka last year, was earlier ruled out the India A squad for the ongoing unofficial limited-overs series against West Indies A due to injury.
The Challenger Trophy played between three teams -- India Blue, India Red and India Green -- will be played in Indore from September 26-29.