The current therapeutic strategies for non-small cell lung cancer (NSCLC) are limited and unsatisfactory. MicroRNAs (miRNAs) participate in tumor angiogenesis in NSCLC. The aim of this study was to investigate the role of miR-20a-5p (miR-20a) in human NSCLC metastasis. In the current study, bioinformatics analysis and RT-PCR were performed to examine the expression level of miR-20a in tissues of NSCLC patients and NSCLC cell lines, respectively. Western blot was performed to test the protein levels. Cell proliferation, migration and angiogenesis capacity were tested by 5-ethynyl-29-deoxyuridine (EdU) assay, transwell assay and tube formation assay, respectively. Dual-luciferase reporter assay (DLR) was used to confirm the interaction between miR-20a and paired ribonucleotide reductase regulatory subunit M2 (RRM2). We found that the expression of RRM2 was upregulated, while the expression of miR-20a was downregulated in cancer tissues compared with adjacent tissues in NSCLC patients. We also detected the expression level of RRM2 and miR-20a in NSCLC cell lines, showing A549 cell line exhibited the lowest expression level of miR-20a and highest expression level of RRM2. Overexpressed miR-20a not only dramatically suppressed NSCLC cells proliferation, endothelial cells migration and tube formation in vitro, but also inhibited tumor growth and angiogenesis in vivo. It was demonstrated that miR-20a suppressed NSCLC growth by inhibiting RRM2-mediated PI3K/Akt signaling pathway. These findings indicate that the novel identified miR-20a could function as a tumor suppressor in NSCLC through modulating the RRM2-mediated PI3K/Akt axis, and it could be a valid molecular target for NSCLC treatment.