Abstract: Objective To investigate the effect of miR-204 on the invasion and metastasis of breast cancer by targeted regulation of HNRNPA2B1. Methods The bioinformatics database was used to obtain data of the expressions of miR-204 in breast cancer patients and the survival rate of the patients. RT-qPCR was used to detect the expression of miR-204 in breast cancer cell lines. The expression vector GV369-miR-204 was used to overexpress miR-204 in MDA-MB-231 cells. Transwell assay was performed to detect the effect of miR-204 on the migration and invasion ability of the breast cancer cells. The key genes (hub genes) of miR-204 were determined by bioinformatics method. A dual luciferase assay was used to analyze the targeting relationship between miR-204 and HNRNPA2B1. The expression of HNRNPA2B1 in MDA-MB-231 cells after miR-204 overexpression was detected by Western blotting, and Transwell assay was used to examine the changes in the cell invasion ability. Results The expression of miR-204 was decreased in both breast cancer tissues, and was significantly lower in breast cancer MDA-MB-231 cells than in MCF-10A cells (P<0.05). The decreased expression of miR-204 was associated with poorer prognosis of breast cancer patients (P<0.05). Upregulation of miR-204 in MDA-MB-231 cells significantly inhibited the invasion and migration of the cells (P<0.05). Analysis of the data from the Starbase revealed that the expression of miR-204-5p was negatively correlated with the expression of HNRNPA2B1, and the expression of HNRNPA2B1 was increased in breast cancer patients (P<0.05) in association with a poorer prognosis of the patients (P<0.05). Dual luciferase assay demonstrated that miR-204 could bind to HNRNPA2B1 in a target-specific manner. Western blotting and Transwell assay showed that miR-204 significant inhibited the migration and invasion ability of breast cancer cells by targeting HNRNPA2B1 (P<0.05). Conclusion miR-204 expression is decreased in breast cancer tissues and cells, and its overexpression can inhibit the invasion and metastasis of breast cancer cells by targeted regulation of HNRNPA2B1.