Background <p>GTPase, IMAP family genes (GIMAPFGs) are extensively used for diagnosis and treatment in cancer, their prognostic significance and therapeutic potential in hepatocellular carcinoma (HCC) remain insufficiently explored.</p> Methods <p>GIMAPFGs associated with HCC prognosis were identified using Cox regression analysis. a prognostic model was constructed through multivariate Cox regression, the model was validated on an independent dataset. followed by an analysis of its biological function. We analyzed variations in tumor immune cell infiltration according to the prognostic signature. Meanwhile, single-cell analysis demonstrated the expression of GIMAPFGs in HCC.</p> Results <p>A prognostic risk model was developed using 2 GIMAPFGs (GIMAP1 and GIMAP8) and its prognostic significance was confirmed with an independent external HCC dataset, establishing it as an independent risk factor for HCC patients. This characteristic is also associated with the immune microenvironment of HCC.</p> Conclusions <p>This novel GIMAPFGs signature provides a valuable tool for patient stratification and offer a new therapeutic approach for HCC.</p>