Objective To study the effect of miR-141 on the proliferation of head and neck squamous cell carcinoma(HNSCC)cells. Methods The expressions of miR-141 in 19 HNSCC tissues and the matched adjacent normal tissues were analyzed by qRT-PCR. The miR-141 in Hep-2 or SCC-9 cells was overexpressed or down-regulated by miR-141 mimics or miR-141 ASO transfection. Then the effects of overexpression or down-regulation of miR-141 on cellular proliferation were analyzed by MTT experiment. The targeted genes of miR-141 were predicted by bioinformatics algorithms. Results The expression of miR-141 in HNSCC tissues was found significantly lower than that in matched normal tissue(P<0.05). Overexpression of miR-141 significantly inhibited the proliferation of Hep-2 and SCC-9 cells, and down-regulation of miR-141 significantly promoted the proliferation of Hep-2 and SCC-9 cells(P<0.05). Bioinformatics algorithms showed that ZEB1 was likely to be a targeted gene of miR-141 in HNSCC. Conclusion miR-141 may inhibit HNSCC cell proliferation via ZEB1.