【Abstract】 Objective To investigate whether miR-129-5p could regulate the sensitivity of lung cancer cells to cisplatin (DDP) by regulating the expression of Larelated protein 1 (LARP1). Methods The expression levels of miR-129-5p, LARP1 and multidrug resistanceassociated protein (MRP1) in lung cancer cells A549 and lung cancer cisplatinresistant cells A549/DDP were detected by realtime quantitative PCR and Western blot. A549/DDP cells were divided into control (NC), miRcon, miR-129-5P, si-con, si-LARP1, miR-129-5p+pcDNAcon and miR-129-5p+pcDNA-LARP1 groups. The cell counting kit (CCK-8) was used to detect cell viability and the halfinhibitory concentration (IC50) against cisplatin. Western blot detected the expression levels of CyclinD1 and MRP1 proteins. The dual luciferase reporter gene assay and Western blot assay were used to verify the targeted and regulatory relationship between miR-129-5p and LARP1. Results Compared with A549 cells, the expression level of miR-129-5p was decreased in A549/DDP cells, while the expression levels of LARP1 and MRP1 were increased, the difference was statistically significant (P＜0.05). Compared with miRcon group, A549/DDP the cell survival rate and IC50 of A549/DDP cells in miR-129-5p group were decreased, and expression of CyclinD1 and MRP1 proteins were decreased, the difference was statistically significant(P＜0.05). Compared with the si-con group, the survival rate and IC50 of A549/DDP cells in the si-LARP1 group were decreased, and the expression of CyclinD1 and MRP1 proteins were decreased, the difference was statistically significant (P＜0.05). Compared with miR-129-5p+pcDNAcon group, the survival rate and IC50 of A549/DDP cells in the miR-129-5p+pcDNA-LARP1 group were increased, and the expression of CyclinD1 and MRP1 proteins were increased, the difference was statistically significant (P＜0.05). LARP1 was the target gene of miR-129-5p. LARP1 protein expression was decreased after overexpressing miR-129-5p, whereas LARP1 protein expression was increased after silencing miR-129-5p, the difference was statistically significant (P＜0.05). Conclusion miR-129-5p inhibits the proliferation of lung cancer cells and increases its cisplatin sensitivity by targeting downregulation of LARP1 expression.