background: The functions of microRNAs (miRNAs) in cancer progression have been recognized in recent years. However, the role of miR-4319 in esophageal squamous cell carcinoma (ESCC) remains unclear. objective: We aimed to investigate the biological roles of miR-4319 in ESCC progression and the associated mechanisms. methods: Real-time PCR was performed to examine the levels of miR-4319 in ESCC cell lines. The effects of miR-4319 and NOD-like receptor (NLR) family, caspase activation and recruitment domain (CARD) domain containing 5 (NLRC5) on cell proliferation and cell cycle progression were evaluated using MTT assay, colony formation and flow cytometry assays. Bioinformatics techniques and luciferase reporter assay were applied to validate NLRC5 as a miR-4319 target. results: The miR-4319 expression was lower in ESCC cells than in the normal cell line. The expression of miR-4319 repressed cell growth and induced cell cycle arrest. NLRC5 was validated as a direct downstream target of miR-4319. Overexpression of NLRC5 potentiated the effects of miR-4319 on cell growth and cell cycle distribution. conclusions: Our results demonstrated that miR-4319 might function as a tumor suppressor by targeting NLRC5 in ESCC.