Spermatogenesis-associated protein 2 (SPATA2) is primarily named for its important role in spermatogenesis. Its function in tumorigenesis remains elusive. Here, we used various bioinformatic tools to systematically analyze the expression patterns of SPATA2 in cancers, the correlation of SPATA2 expression with clinical parameters, genetic variation, methylation, phosphorylation, immune infiltration and immune therapy. SPATA2 is significantly upregulated in multiple cancers and its expression was associated with tumor stage, grade and serve as a potential prognostic marker in LIHC. Notably, SPATA2 was also linked to immune suppression, exhibiting positive correlations with immune checkpoint genes and immune suppressive cells such as regulatory T cells and MDSCs. Furthermore, SPATA2 interacted and co-expressed with proteins involved in DNA repair mechanisms, indicating its potential role in maintaining genomic stability. Finally, we conducted biological experiments to investigate the role of SPATA2 in LIHC. SPATA2 knockdown enhances the migration and proliferation capabilities of Hep-G2 and HuH7 cell lines. These findings underscore the significance of SPATA2 in cancer biology, suggests its role in both the tumor microenvironment and the tumor cell level and its potential as a prognostic marker and therapeutic target in oncology, particularly in LIHC.