ObjectiveTo investigate the expression of gasdermin (GSDM) gene family in primary liver cancer and its clinical significance. MethodsThe Gene Expression Profile Data Dynamic Analysis (GEPIA2) database was used to analyze the expression levels of GSDM gene family in primary liver cancer and normal tissues, and survival analysis was performed to explore its relationship with prognosis; GEPIA2 database was used to explore the relationship between GSDM gene family and TNM staging of patients with primary liver cancer. We used GeneMANIA database to predict genes that may interact with GSDM gene family, and used Metascape website for functional enrichment analysis. Finally, we used TIMER database to explore the relationship of expression of GSDM gene family and immune cell infiltration in the tumor microenvironment of primary liver cancer. ResultsCompared with normal liver tissues, GSDMA, GSDMC, GSDMD, and GSDME were highly expressed in primary liver cancer (P<0.050), and GSDMB and DFNB59 were low expressed (P<0.050); results of univariate Cox proportional hazard regression model showed that the differential expressions of GSDMD, GSDME, and DFNB59 were related to the overall survival of patients (P<0.050), and the results of the multivariate Cox proportional hazard regression model showed that GSDME could be used as an independent predictor of the prognosis of liver cancer patients (P<0.050). With the increase of TNM staging in patients with liver cancer, the expressions of GSDMA and GSDMC also gradually increased (P<0.050). Further enrichment analysis showed that the GSDM gene family was involved in pyrolysis and various immune-related biological processes. ConclusionThe GSDM gene is differentially expressed in primary liver cancer, participates in immune-related biological processes, and its expression is related to clinicopathological staging and patients’ prognosis.