摘要Objective There are several reports that suggest a significant role played by microRNAs (miRNAs) in cell invasion, metastasis, differentiation, and apoptosis in lung cancers. miR-375 is one such miRNA that has been detected in a variety of tumors, but its specific activity in non-small cell lung cancer (NSCLC) remains unclear. Methods In this study, we regulated the expression of miR-375, to evaluate its influence on the 14-3-3ζ/ ERK/MYC pathway in NSCLC. Results The results of our experiments suggest that miR-375 and 14-3-3ζ are highly expressed in NSCLC, and the over-expression of miR-375 increases the invasive, metastatic, and proliferative ability and decreases the apoptotic ability of NSCLC cells. In addition, protein expression levels of 14-3-3ζ, p-ERK, and MYC increased following the overexpression of miR-375. Conclusion Overall, our findings indicate that miR-375 increases the malignant potential of NSCLC via the 14-3-3ζ/ERK/MYC pathway.