An endogenous H2S-triggered intelligent optical nanoprobe combining second near-infrared (NIR-II) fluorescence with photoacoustic (PA) imaging can provide more comprehensive information to further improve the sensitivity and reliability of diagnosis for colorectal tumor, which is rarely explored. Herein, an endogenous H2S-triggered SiO2@Ag nanoprobe was designed for in situ dual-modal NIR-II/PA imaging of colorectal cancer. The designed dual-modal nanoprobe can be converted to SiO2@Ag2S after in situ biosynthesis via a sulfuration reaction with the over-expressed endogenous H2S in the colorectal tumor. More importantly, the designed SiO2@Ag nanoprobe exhibits high sensitivity and specificity for diagnosing colorectal cancer in vivo via dual-modal NIR-II/PA imaging. These results provide a new NIR-II/PA dual-modal imaging strategy for noninvasive intelligent detection of colorectal cancer.