Heterogeneous nuclear ribonucleoprotein A2B1 (HNRNPA2B1), a member of the A/B subfamily of hnRNPs, plays a critical role in tumorigenesis, yet its expression patterns, molecular mechanisms, and prognostic significance remain inadequately characterized. In this study, we performed a comprehensive pan-cancer analysis utilizing multiple public databases, revealing that HNRNPA2B1 is consistently overexpressed in most tumor types and correlates with poor prognosis across several malignancies. Pathway enrichment analysis highlighted its involvement in RNA alternative splicing, transport, and stability, processes that contribute to tumor progression. Epigenetic analyses identified gene amplification and alternative splicing as potential mechanisms driving HNRNPA2B1 overexpression. Furthermore, elevated HNRNPA2B1 levels conferred resistance to multiple chemotherapeutics, including Dasatinib. Functional studies demonstrated that HNRNPA2B1 enhances lung cancer cell proliferation and migration by upregulating TARDBP and cell cycle-related genes, with m6A modification serving as a critical regulatory mechanism. Collectively, these findings establish HNRNPA2B1 as an oncogenic factor across multiple cancer types, underscoring its value as a prognostic marker and a promising therapeutic target, particularly in lung cancer, offering new insights for targeted therapeutic strategies.