〔Abstract〕 Objective To explore the effects of miR-381 on proliferation and invasion of gastric cancer cells by targeting transmembrane protein 16 A(TMEM16 A) and its mechanism. Methods 34 gastric cancer patients who underwent surgical resection were enrolled. Their cancer tissues and adjacent normal tissues(less than 3 cm away from the cancer) were collected. The gastric cancer cells AGS, MKN45 and SGC7901, and normal human gastric mucosal cells GES-1 were cultured. The expression of miR-381 in tissues and cells was detected by qRT-PCR. The miR-381-mimics and TMEM16 A-siRNA were transfected into AGS cells. The blank control group was set up. The expression of miR-381 and TMEM16 A mRNA in cells was detected. The targeted relationship between miR-381 and TMEM16 A was analyzed by online bioinformatics prediction software and dual-luciferase reporter assay. The cell proliferation was detected by MTT assay. The apoptosis was detected by flow cytometry. The cells invasion ability was detected by Transwell chamber. The expression of p27 gene, cysteine-containing aspartate proteolytic enzyme(caspase-3, caspase-9), E-cadherin, Vimentin and matrix metalloproteinase(MMP-2, MMP-9) in cells was detected by Western blot. Results Compared with normal tissues and normal gastric mucosa cells, the expression of miR-381 in gastric cancer tissues and cells decreased(P<0.05), while expression of TMEM16 A mRNA increased(P<0.05).Compared with blank control group, the expression of miR-381 increased, while the expression of TMEM16 A mRNA decreased in miR-381-mimics group(P<0.05), the expression of TMEM16 A mRNA decreased in TMEM16 A-siRNA group(P<0.05), and the expression of miR-381 increased in combination transfection group(P<0.05). However, there was no significant difference compared with that in miR-381-mimics group(P>0.05). The expression of TMEM16 A mRNA decreased(P<0.05), which was lower than that in miR-381-mimics group and TMEM16 A-siRNA group(P<0.05). Compared with blank control group, cell proliferation in miR-381-mimics group, TMEM16 A-siRNA group and combination group was significantly inhibited, the apoptosis and the expression of p27, caspase-3, caspase-9 and E-cadherin increased, while the number of cell invasion, expression of Vimentin, MMP-2 and MMP-9 decreased(P<0.05). Conclusion MiR-381 can inhibit proliferation and invasion of gastric cancer AGS cells by negatively regulating TMEM16 A, and promote their apoptosis.