Prostate cancer (PCa) is a prevalent malignant disease and the primary reason for cancer-related mortality among men globally. GLIS1 (GLIS family zinc finger 1) is a key regulator in various pathologies. However, the expression pattern, clinical relevance, and immunomodulatory function of GLIS1 in PCa remain unclear. In this study, GLIS1 was discovered to serve as a key gene in PCa by integrating mRNA and miRNA expression profiles from GEO database. We systematically explored the expression and prognostic values of GLIS1 in cancers using multiple databases. Additionally, we examined the functions of GLIS1 and the relationship between GLIS1 expression levels and immune infiltration in PCa. Results showed that GLIS1 was differentially expressed between normal and tumor tissues in various cancer types and was significantly low-expressed in PCa. Low GLIS1 expression was associated with poor PCa prognosis. GLIS1 was also involved in the activation, proliferation, differentiation, and migration of immune cells, and its expression showed a positive correlation with the infiltration of various immune cells. Moreover, GLIS1 expression was positively associated with various chemokines/chemokine receptors, indicating the involvement in regulating immune cell migration. In summary, GLIS1 is a potential prognostic biomarker and a therapeutic target to modulate anti-tumor immune response in PCa.