To study the effects of cucurbitacin Ⅱ combined with trametinib on the colorectal cancer cells HT-29 apoptosis and epithelial-mesenchymal transition(EMT) through miR-4319.Methods:Colorectal cancer cells HT-29 were divided into 6 groups，namely the a control group，a trametinib group，a coprininoside II group，a combination group，an miR-NC inhibition group，and an miR-4319 inhibition group(n＝9).In 6 groups，CCK-8 experiment was used to detect cell proliferation，flow cytometry was used to detect cell apoptosis，Western blot was used to detect the protein expression of Vimentin，E-cadherin，Bax，and C-Caspase-3，and the expression of miR-4319 was detected by qRT-PCR.Compare the experimental results of the 6 groups.Results:Compared with the control group，the cell survival rate，and the expression of Vimentin in the trametinib group，the berberine Ⅱ group and the combination group were reduced(P<0.05)，while the apoptosis rate and the expression of Bax，C-Caspase-3，E-cadherin both increased(P<0.05); compared with the miR-NC inhibition group，the cell survival rate and Vimentin expression in the miR-4319 inhibition group were significantly increased(P<0.05).However，the apoptosis rate，the expression of Bax，C-Caspase-3 and E-cadherin were significantly reduced(P<0.05); qRT-PCR results showed that compared with the control group，the expression of miR-4319 in the cells of the trametinib group and berberineⅡgroup increased(P<0.05).Conclusion:The combination of cucurbitacin Ⅱ and trametinib induces the apoptosis and inhibits cell EMT of colorectal cancer cells HT-29 by up-regulating miR-4319.