Background: Aberrant expression of RNA-binding proteins (RBPs) has been linked to a variety of diseases, including hematological disorders, cardiovascular diseases, and multiple types of cancer. Heterogeneous nuclear ribonucleoprotein C (HNRNPC), a member belonging to the heterogeneous nuclear ribonucleoprotein (hnRNP) family, plays a pivotal role in nucleic acid metabolism. Previous studies have underscored the significance of HNRNPC in tumorigenesis; however, its specific role in malignant tumor progression remains inadequately characterized. Methods: We leveraged publicly available databases, including The Cancer Genome Atlas (TCGA), to explore the potential involvement of HNRNPC across various cancers. Additionally, we performed experimental validation studies focused on liver cancer. Results: Our analysis revealed that HNRNPC is overexpressed in a wide range of common malignancies, including liver and lung cancers, and is strongly linked to unfavorable outcomes. Furthermore, HNRNPC was observed to be closely linked to tumor immunity. Through immune checkpoint analysis and immune cell infiltration assessment, HNRNPC emerged as a potential target for modulating tumor immunotherapy. Notably, silencing of HNRNPC markedly inhibited the proliferation, metastasis, and infiltration of liver cancer cells. Conclusion: In summary, our fi ndings highlight HNRNPC as a prognostic marker in various cancers, including liver cancer, and suggest its involvement in shaping the tumor immune microenvironment. These insights offer potential avenues for improving clinical outcomes in tumors with elevated HNRNPC expression, particularly through immunotherapeutic strategies.