Immunogenic cell death (ICD) inducers are valuable chemotherapeutic agents that elicit protective immune responses against tumors. However, the specific molecular targets directly associated with ICD remain less explored. Here, a Type II ICD inducer, Pt-ER, was validated as a bona fide ICD inducer with the ability to establish protection against colorectal cancer. Based on Pt-ER, several ICD-inducing photoactivable probes were designed to capture their potential targets. By integrating quantitative proteomics analysis, genetic method and biochemical assays, we identified that PTP1B is a direct target of Pt-ER and engages in ICD.