Heterogeneous nuclear ribonucleoprotein A2, as an RNA binding protein, participates in the processing and metabolism of RNA molecules. HnRNPA2 is overexpressed in a variety of cancer cells and promotes cancer cell proliferation, which is a potential drug target for tumor therapy. However, few ligands that specifically target A2 protein and inhibit its function have been reported. In this study, a variety of small molecule compounds that can interact with A2 protein were screened from natural and synthetic compounds libraries using computer virtual screening technology and BIAcore high-throughput screening system. In many ways, such as isothermal tiorimetry calorimetry, fluorescence quenching assay, molecular docking simulation and cellular thermal shift assay, we confirmed the interactions between small molecule compounds EpimedinA1, G38 and hnRNPA2 proteins, respectively. Cell experiments showed that G38 inhibited the proliferation of MCF-7 cells and MDA-MB-231 cells in a dose-dependent manner. Furthermore, A2 knockout in breast cancer cells significantly down-regulated cell sensitivity to G38, suggesting that G38 targets A2 protein and inhibits cell proliferation. Our study identified a number of small molecule compounds that may bind to A2 protein and confirmed that G38 inhibits the proliferation of breast cancer cells by binding hnRNPA2 protein, providing a potential targeted drug for clinical treatment of hnRNPA2 overexpressed diseases.