MicroRNAs (miRNAs) play important roles in some human malignancies. The dysregulation of miR-202-3p has been identified to correlate with tumor proliferation and apoptosis in various tumors. However, its biological function and regulatory mechanism in NSCLC remain largely unknown. This study aimed to investigate the biological role and underlying mechanism of miR-202-3p in human NSCLC. Real-time quantitative PCR (RT-qPCR) revealed that miR-202-3p expression was decreased in NSCLC tissues and cells. RT-qPCR and Western blotting revealed that mucin 4 (MUC4) expression was significantly increased in NSCLC cells. Overexpression of miR-202-3p suppressed cell proliferation and induced apoptosis in both A549 and H292 cells. Additionally, overexpression of miR-202-3p induced apoptosis by regulating apoptosis associated BCL-2/caspase-3 pathway. Furthermore, miRNA target databases and luciferase reporter assay confirmed that MUC4 was a direct target gene of miR-202-3p in NSCLC. In conclusion, our results suggested that miR-202-3p may function as a tumor suppressor in human NSCLC by directly targeting MUC4.