Background Immunogenic cell death (ICD) is a type of regulated cell death that is sufficient to trigger an adaptive im-mune response. ICD has been demonstrated to activate the tumor-specific immune response, and inducing ICD would be a potential treatment strategy. Aims The biomarkers of ICD and their relationships with tumor microenvironment, clinical feathers, and immunotherapy response are not fully understood in the context of the clinic. We therefore conducted pan-cancer analyses of ICD gene signatures in 33 cancer types from The Cancer Genome Atlas database. Methods and results We identified key genes that had strong relationships with survival and tumor microenvironment. Besides, we predicted therapeutic agents targeting ICD genes and explored the potential mechanisms of gemcitabine to induce ICD. Moreover, we determined an ICD score based on the ICD genes and found that the ICD score was associated with patient prognosis, clinical features, tumor microenvironment, radiotherapy access, and immunotherapy response. The high ICD score was associated with the immune-hot phenotype, and the low ICD score was associated with the immune-cold phenotype. Conclusion We discovered the potential of the ICD gene signatures as ICD biomarkers in pan-cancer, which may provide new insights into immuno-phenotypic assessment and cancer therapeutic strategies, allowing more patients to benefit from immunotherapy.