Mutation count > 11 (tumor mutation burden (TMB)-high), age > 65, male, RNF43, CREBBP, NOTCH3, PTCH1, CIC, DNT1, and SPEN mutant (MT) were associated with longer OS, while APC-mMT and TP53-MT were significantly correlated with shorter OS….Our study is the first to elucidate comprehensive prognostic factors for the treatment of ICIs in CRC patients, from clinical characteristics such as age and sex to specific gene mutations, providing new ideas for immunotherapy in CRC.