〔Abstract〕 Objective To investigate the effect and mechanism of miR-145-3p on mitophagy in 1-methyl-4-phenylpyridiniumion(MPP+)-induced Parkinson′s disease(PD) cell model. Methods Human neuroblastoma cells(SH-SY5Y) were divided into control group, model group, mimics group, calmodulin-dependent protein kinase kinaseβ(CaMkkβ) inhibitor(STO-609) group, mimics+STO-609 group, cyclic adenosine monophosphate response element-binding protein(CREB) inhibitor(KG-501) group, mimics+KG-501 group and STO-609+KG-501 group. Cell apoptosis was detected by flow cytometry, autophagosome structure was observed by transmission electron microscopy, and apoptosis, autophagy and CaMkkβ/adenylate activated protein kinase(AMPK)/CREB pathway related protein expression were detected by Western blot. Results Compared with control group, the apoptosis rate, Bcl-2-associated X protein(Bax), cysteine proteinase-3(Caspase-3) and microtubule-associated protein light chain 3-I(LC3-Ⅰ) protein expression levels in model group increased(P<0.01), and the autophagosome structure decreased. The protein levels of B cell lymphoma-2(Bcl-2), autophagy gene(Beclin-1), microtubule-associated protein light chain 3-Ⅱ(LC3-Ⅱ), phosphorylated calmodulin-dependent protein kinase kinaseβ(p-CaMkkβ), phosphorylated cadenylate activated protein kinase(p-AMPK), and phosphorylated cyclic adenosine monophosphate response element-binding protein(p-CREB) decreased(P<0.01). Compared with model group, the apoptosis rate, Bax, Caspase-3 and LC3-Ⅰ protein expression levels in mimics group decreased(P<0.05), and the autophagosome structure increased. The protein levels of Bcl-2, Beclin-1, LC3-Ⅱ, p-CaMkkβ, p-AMPK, p-CREB increased(P<0.05). The trend of STO-609 group and KG-501 group was the same and opposite to mimics group. Compared with mimics group, the apoptosis rate, Bax, Caspase-3 and LC3-Ⅰ protein expression levels in the mimics+STO-609 group and the mimics+KG-501 group increased(P<0.01), and the autophagosome structure decreased. The protein levels of Bcl-2, Beclin-1, LC3-Ⅱ, p-CaMkkβ, p-AMPK, p-CREB protein levels decreased(P<0.01). Compared with STO-609 group, the apoptosis rate, Bax, Caspase-3 and LC3-Ⅰ protein expression levels of STO-609+KG-501 group increased(P<0.01), and the autophagosome structure decreased. The protein levels of Bcl-2, Beclin-1, LC3-Ⅱ, p-CaMkkβ, p-AMPK and p-CREB decreased(P<0.05). Conclusion miR-145-3p can inhibit the apoptosis of MPP+-induced PD cell model and promote mitophagy, and its mechanism may be related to the activation of the CaMkkβ/AMPK/CREB pathway.