Numerous studies have indicated that STAT3 plays a key role in promoting oncogenesis and it is considered a potential therapeutic target for cancer treatment; however, there are no reports on STAT3 using pan-cancer analysis. Therefore, it is important to investigate the role of STAT3 in different types of tumors using pan-cancer analysis. In the present study, we used multiple databases to comprehensively analyze the relationship between STAT3 expression and prognosis, different stages of patients with cancer, investigate the clinical value of STAT3 in predicting prognosis, and the relationship between STAT3 genetic alteration and prognosis, drug sensitivity, and STAT3 expression, to determine whether STAT3 participates in tumor immunity, to provide a rationale for STAT3 as a treatment target for a broad-spectrum malignancies. Our results indicate that STAT3 can serve as a prognostic, sensitivity prediction biomarker and a target for immunotherapy, which has been of great value for pan-cancer treatment. Overall, we found that STAT3 significantly predicted cancer prognosis, drug resistance, and immunotherapy, providing a rationale for further experimental studies.