Previous study has shown heterogeneous nuclear ribonucleoprotein A1(HNRNPA1) is highly expressed in various human cancers. In order to study the clinical value and potential function of HNRNPA1 in HBV-related hepatocellular carcinoma (HCC), three datasets from the GEPIA, GEO and TCGA were analyzed. HNRNPA1 expression was found to be significantly higher in HBV-positive HCC samples, which was supported with IHC validation. Both GO and KEGG analyses demonstrated that HNRNPA1 co-expressed genes were involved in translation, ribonucleoprotein complex biogenesis and assembly, ribosome biogenesis, RNA processing, RNA splicing, etc. Survival analysis showed a significant reduction in overall survival of patients with high HNRNPA1 expression from both the GSE14520 cohort and 151 patients with HBV-related HCC cohort. Furthermore, Gene set enrichment analysis (GSEA) revealed that HNRNPA1 may regulate HCC progression by influencing the cell cycle and WNT signaling pathway, etc. HNRNPA1 overexpression has diagnostic value in distinguishing between HCC and non-HCC liver tissue (AUC = 0.730). Finally, HNRNPA1 was a directly target gene of miR-22 manifested by the reduced luciferase activity and decreased HNRNPA1 expression in the cells with overexpression of miR-22. HNRNPA1 might function as an oncogene through the EGFR signaling pathway in HBV-related HCC, which has not been reported in previous studies.