MicroRNAs (miRNAs) function as key regulators of numerous types of cancers. miRNA (miR)‑421 expression is dysregulated in a variety of tumors; however, its role in non‑small cell lung cancer (NSCLC) remains unclear. In the present study, the role and molecular mechanism of miR‑421 in NSCLC was investigated. In this study, miRNA (miR)‑421 was upregulated in NSCLC tissues and cell lines used the reverse transcriptase quantitative polymerase chain reaction. Ectopic expression of miR‑421 significantly promoted cell proliferation in vitro and tumor growth in vivo by promoting cell cycle progression via CCK-8, colony formation, EdU assay, xenograft model and cell cycle assay. In addition, miR‑421 inhibited NSCLC cell apoptosis by flow cytometry apoptosis assay, as evidenced by anti‑apoptosis gene Bcl‑2 and apoptosis gene cleaved caspase‑3 and cleaved PARP using western blot assay. Furthermore, miR‑421 promoted cell migration and invasion through EMT process using Transwell and western blot assay. It was also demonstrated that miR‑421 can directly target HOPX by the EGFP reporter assay and western blot assay. MiR‑421 overexpression promoted the protein expression levels of β‑catenin, cyclin D1 and c‑myc by western blot assay, which are the downstream genes of Wnt pathway. These data indicated that miR‑421 may act as an oncogene through the effects of HOPX on the Wnt/β‑catenin signaling pathway and may provide insight into the mechanisms underlying carcinogenesis and the identification of potential biomarkers associated with NSCLC.