〔Abstract〕 Objective To investigate the effect of miR-33-5 p on the regulation of c-Jun amino terminal kinase 1(JNK1) on the multi-drug resistance of human oral squamous cell carcinoma. Methods CAL-27 cells were divided into CAL-27 group,CAL-27/CBP group,CAL-27/CBP+ scramble inhibitor group,CAL-27/CBP+ miR-33-5 p inhibitor group,carboplatin(CBP) induced drug resistance Cell line,according to the group transfected with scramble inhibitor or miR-33-5 p inhibitor.MTT detected the multi-drug resistance of cells,RT-PCR detected the expression of miR-33-5 p,luciferase report test detected miR-33-5 p With JNK1 targeting,Western blot was used to detect the activation of the JNK1/c-Jun pathway and the expression of MDR1,and flow cytometry was used to detect the results of Rh123 aggregation. Results Compared with CAL-27 group,the multi-drug resistance of CAL-27/CBP increased(P<0.01),the expression level of miR-33-5 p increased(P<0.01),and the activation level of JNK1/c-Jun pathway decreased(P<0.01),the percentage of Rh123 positive cells decreased(P<0.01),the level of MDR1 protein increased(P<0.01),and the luciferase reported experimental results showed that miR-33-5 p targeted JNK1; compared with the CAL-27/CBP group,the multi-drug resistance of cells in the CAL-27/CBP+miR-33-5 p inhibitor group reduced(P<0.05),the expression level of miR-33-5 p reduced(P<0.01),The activation level of JNK1/c-Jun pathway increased(P<0.01),the percentage of Rh123 positive cells increased(P<0.01),and the level of MDR1 protein decreased(P<0.01). Conclusion MiR-33-5 p reduces the multi-drug resistance of CAL-27/CBP drug-resistant cell lines through targeted regulation of JNK1/c-Jun pathway.