Lung cancer (LC), as the most common cause of cancer-related mortality worldwide, is characterized by difficulties in early detection, a high degree of malignancy, poor sensitivity to radiotherapy and chemotherapy, and a low 5-year survival rate. MicroRNA (miRNA) is a class of small, non-coding, endogenously expressed RNA that serves vital roles in RNA silencing and post-transcriptional regulation of gene expression. Previous studies have shown that abnormal expression of miRNA is relevant to various malignant tumors, including lung cancer. In the present study, miR-150 was found to be significantly upregulated in non-small cell lung cancer (NSCLC) cells, which also exhibited downregulation of SIRT2. Through downregulation of miR-150 and/or overexpression of SIRT2 in NSCLC cells (A549 and H1299), in vivo assays revealed that the suppression of miR-150 and re-expression of SIRT2 could inhibit NSCLC cell growth. Additionally, the present data demonstrated that miR-150 regulated NSCLC cell viability and mobility through SIRT2/JMJD2A. Finally, it was demonstrated that silencing of miR-150 led to inactivation of the AKT signaling pathway, which eventually inhibited the viability and mobility of NSCLC cells. This inhibitory effect of miR-150 could be exacerbated by upregulation of SIRT2. In conclusion, our results demonstrated that miR-150 plays an important role in the development of lung cancer by serving as an oncogene via the SIRT2/JMJD2A signaling pathway.