Lung cancer is the most aggressive cancer with the highest mortality and incidence rates worldwide. microRNAs have been identified as potential targets for non-small cell lung cancer (NSCLC) treatment. However, the modulatory role of miR-514b-5p in NSCLC progression is little known. Herein, miRNA expression datasets for NSCLC were downloaded from the Cancer Genome Atlas and Gene Ontology Omnibus databases. Gene expression was assessed using qRT-PCR, and western blot analysis, and immunohistochemical (IHC) staining was used to determine protein expression. Gain and loss of function experiments were performed to investigate the impact of miR-514b-5p and small glutamine-rich tetratricopeptide repeat-containing protein beta (SGTB) on cell proliferation and apoptosis. RNA immunoprecipitation (RIP) and dual-luciferase assays were performed to analyze the target gene of miR-514b-5p. The biological roles of miR-514b-5p were lastly evaluated using nude mouse tumorigenicity assays in vivo. We found that miR-514b-5p was dramatically increased in NSCLC tissues and higher miR-514b-5p expression was associated with poorer overall survival in NSCLC patients. Furthermore, overexpression of miR-514b-5p promoted NSCLC cell growth and suppressed apoptosis by inducing the activation of the PI3K/AKT and p38 signaling pathways. Mechanistically, dual-luciferase and RIP results highlighted that SGTB was a target gene of miR-514b-5p. Moreover, overexpression of SGTB reduced cell division and promoted apoptosis in vitro through blocking the PI3K/AKT and p38 signaling pathways. Our findings indicated that miR-514b-5p contributes to carcinoma progression in NSCLC via the PI3K/AKT and p38 signaling pathways by targeting SGTB and this could be a promising diagnostic and therapeutic target for the treatment of NSCLC.This article is protected by copyright. All rights reserved.