It's a huge challenge to develop effective nanosystems that combine the capabilities of diagnoses and therapies together for colon cancer in the clinic. Herein, we constructed a far-red absorbing phototheranostic nanosystem (FR-H2S) based on the thiolytic reaction of a dinitrophenyl modified phototheranostic prodrug and over-expressed H2S in colon cancer sites for precise imaging-guided phototherapy. FR-H2S with a BODIPY core not only could work as an imaging probe for diagnosis but also act as a phototherapeutic agent for cancer treatment under a single FR laser source (650 nm). FR-H2S exhibited a gradually enhanced fluorescence emission for precise diagnosis of H2S-rich colon tumor sites. After entering tumor cells, FR-H2S could generate abundant 1O2 and heat for phototherapies timely by using the same laser source (650 nm). We believe that this precise imaging-guided phototheranostic nanosystem could provide a promising approach to colon cancer with minimal damage.