CGB5 plays an important factor in numerous different cancers and is strongly associated with patient prognosis. Unfortunately, there is currently no data, however, on whether CGB5 plays a role in pan-cancer diseases. Research on CGB5 in pan-cancer has been conducted through multiple websites and public databases, including TCGA, HPA, UALCAN, cbiopportal Platform, UALCAN, GSCA, Kaplan-Meier Plotter, TIMER, TISIDB, SangerBox Website, and metscape. The genomic, transcriptomic, epigenetic, immune microenvironmental, and clinical prognostic significance of CGB5 across pan-cancer is investigated with the resulting outcome. CGB5 expression in gastric cancer was further detected, and the potential mechanism of its influence on prognosis was elucidated. This study found that abnormal CGB5 expression in pan carcinoma is correlated with a poorer prognosis. Aberrant CGB5 expression is potentially linked to gene mutations, copy number variation (CNV), and DNA methylation. In addition, this study revealed a robust association between the expression of CGB5 and immune cell infiltration across various types of cancer, with differences in cell type and level among distinct tumor types. In addition, the present investigation has shown that A strong association has been detected between the upregulation of CGB5 expression and immune cell infiltration in various forms of cancer, with differences in the different tumor types in the type and level of immune cell infiltration. Our further cell experiments also confirmed the upregulation of CGB5 within the context of gastric cancer. In conclusion, it has been noted that CGB5 expression exhibited a substantial rise across wide types of malignancies, and this upregulation was shown to exhibit a significant association with the prognosis of individuals who have cancer. Further studies showed that CGB5 expression in tumors affects the tumor immune microenvironment and promotes tumorigenesis. We also explored CGB5 expression in gastric cancer and clarified its potential prognostic mechanism. It reveals CGB5's significance in cancer diagnosis and treatment.