Background and Aims The Gasdermin (GSDM) family consists of 6 important molecules, which are mainly responsible for regulating various biological processes such as pyroptosis. Recent studies have shown that the expression disorder of the GSDM family is involved in the initiation and development of various types of cancer. However, the expression profiles, prognosis value, related function and potential mechanism of GSDM family in gastric cancer remain to be elucidated. This study was conducted to systematically analyze the role of GSDM members in gastric cancer based on bioinformatics approaches.Methods By databases that included ONCOMINE, GEPIA2, UALCAN, Kaplan-Meier Plotter, cBioPortal, TIMER 2.0, and DiseaseMeth, the expression profiles, prognostic value, function enrichment, gene alterations, association with immune cell infiltration, and methylation status of GSDM family were comprehensively analyzed.Result Only DFNA5 in the GSDM family was significantly highly expressed in gastric cancer, and the expression level is 2.479 times higher than that of normal tissues. The expression level of DFNA5 was significantly increased in subtypes of TNM stages 2, 3, and 4, as well as in subtypes of tumor grades 2 and 3. In the GSDM family, only DFNA5 had prognostic value in gastric cancer, and the high expression of DFNA5 indicated poor overall survival. In the GSDM family, the gene alteration frequency was highest in GSDMD (19%), followed by GSDMA, GSDMB, GSDMC (14%), and lowest in DFNA5 (8%) and PJVK (6%). A total of 186 co-expressed genes of GSDM family were further screened in gastric cancer. These molecules may be involved in the tumorgenesis and development process of gastric cancer through signaling pathways related to inflammatory cell apoptosis, chemokine response, and acute inflammatory response. The expression of most GSDM family members was significantly positively correlated with the infiltration of CD4⁺ T cells, CD8⁺ T cells, B cells, neutrophils, macrophages, and dendritic cells, whereas only PJVK is found to have negative association with macrophages and dendrites. The low methylation status of GSDMA and GSDMD in gastric cancer were also detected.Conclusion The expression and function profiles of GSDM family are disordered in gastric cancer. GSDM family members, especially DFNA5, may have the potential to become essential biomarkers for the diagnosis and prognosis of gastric cancer, as well as provide insight for the development of therapeutic targets.