Objective To investigate effects of capsaicin on proliferation,migration and invasion of human large cell carcinoma NCI-H460 and discuss the possible mechanisms by which capsaicin inhibits non-small cell lung cancer. Methods NCI-H460 cells were cultured in vitro and treated with capsaicin at various concentrations. Colony formation assay,wound healing assay,and transwell chamber invasion assay were used to detect the effects of capsaicin on proliferation,migration and invasion of NCI-H460 cells. Western blotting was used to detect the protein expression of E-cadherin,N-cadherin,Vimentin and Snail. Results The rate of colony formation of 100,200,300 μmol.L-1 of capsaicin were (91.17±24.38)%,(43.22±12.91)% and (15.71±4.26)%,respectively,the control group was (99.53±21.25)%.the rate of migration of NCI-H460 cells of 25,50, 100 μmol.L-1 of capsaicin were (85.83±17.43)%,(37.92±10.16)% and(21.08±6.39)%,respectively,the control group was (93.04±20.23)%.The number of invasion of NCI-H460 cells of 25,50,100 μmol.L-1 of capsaicin were (99±18.2),(75± 17.9) and( 52 ± 14. 1 ) , respectively, the control group was ( 107 ± 20. 4 ) . The middle and high-dose capsaicincould inhibit proliferation,migration and invasion of NCI-H460 cells ( P<0.05) ,and E-cadherin expression level was significantly up-regulated and N-cadherin, Vimentin, Snail expression level was significantly down-regulated ( P<0. 05 ) . Conclusion Capsaicin can inhibit proliferation,migration and invasion of NCI-H460 cells,the mechanism may be related to up-regulation of E-cadherin and down-regulation of N-cadherin,Vimentin and Snail expression levels.