〔Abstract〕 Objective To explore the targeting relationship between miR-106 a-5 p and ERK2 and its effect on cisplatin resistance of gastric cancer cell line MGC-803. Methods RT-PCR was used to detect the expression of miR-106 a-5 p and ERK2 in gastric cancer cell line MGC-803 and drug-resistant cell line MGC-803/DDP. The luciferase reporter assay was used to determine the targeting relationship between miR-106 a-5 p and ERK2. The miR-106 a-5 p mimic and overexpression vector pcDNA3.1-ERK(pc-ERK2) were transfected into drug-resistant cell line MGC-803/cisplatin(DDP), respectively. The cells were divided into control group, miR-106 a-5 p mimic group, ERK2 group and mimic+ERK2 group.Then MTT&EDU were used to measure cell proliferation, hochest33342 was used to observe cell apoptosis, Transwell was used to detect cell invasion. Finally, the expression levels of E-cadherin(E-cad) and N-cadherin(N-cad) in each group of cells were detected by Western blot. Results The expression of miR-106 a-5 p in gastric cancer cell line MGC-803 was significantly higher than that in drug-resistant cell line(P<0.05), while the expression of ERK2 was lower than that in drug-resistant cell line(P<0.05). Secondly, luciferase reporter assays had shown that miR-106 a-5 p targets inhibited ERK2 expression. After transfection with miR-106 a-5 p&pc-ERK2, compared with the control group, the viability, cell proliferation and cell invasion number of ERK2 group significantly increased(P<0.05), and the number of apoptosis significantly decreased(P<0.05); the viability, cell proliferation and cell invasion of the miR-106 a-5 p mimic group were significantly lower than those of the control group(P<0.05), and the number of apoptosis significantly increased(P<0.05). Compared with the ERK2 group, the viability, cell proliferation and cell invasion of the mimic+ERK2 group significantly decreased(P<0.05), and the number of apoptosis significantly increased(P<0.05). Finally, compared with the control group, the expression of E-cad in the miR-106 a-5 p mimic group significantly increased(P<0.05), while the expression of N-cad significantly decreased(P<0.05); meanwhile the expression of E-cad in the ERK2 group significantly decreased(P<0.05), while the expression of N-cad was significantly increased(P<0.05). Compared with the ERK2 group, the expression of E-cad in the mimic+ERK2 group significantly increased(P<0.05), while the expression of N-cad significantly decreased(P<0.05). Conclusion Mir-106 a-5 p can target down-regulate the expression of ERK2 and reduce the drug resistance of gastric cancer cells. It is expected that mir-106 a-5 p can be combined with cisplatin chemotherapy and improve the efficacy of cisplatin chemotherapy.