In the present study, the therapeutic effects and the underlying molecular mechanisms of microRNA (miR)‑145 were investigated in non‑small cell lung cancer (NSCLC) cells. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was performed to examine miR‑145 expression. An MTT assay and flow cytometry were used to investigate cell proliferation and apoptosis, respectively. The protein expression of Bax, epidermal growth factor receptor (EGFR), phosphatidylinositol 3‑kinase (PI3K) and phosphorylated‑protein kinase B (AKT) was examined by western blot analysis. miR‑145 expression was downregulated in patients with NSCLC who were treated with chemotherapy. The downregulation of miR‑145 in A549 cells reduced lactate dehydrogenase (LDH) expression, apoptosis, caspase‑3/-9 levels and Bax protein expression, while it increased cell proliferation. Upregulation of miR‑145 in A459 cells increased LDH, apoptosis, caspase‑3/-9 levels and Bax protein expression, while it inhibited cell proliferation. The EGFR/PI3K/AKT signaling pathway was suppressed by miR‑145 upregulation in A549 cells and induced by miR‑145 downregulation. The EGFR inhibitor suppressed the EGFR/PI3K/AKT signaling pathway and increased the anticancer effects of miR‑145 upregulation in A549 cells. The PI3K inhibitor suppressed the PI3K/AKT signaling pathway and reversed the anticancer effects of miR‑145 upregulation in A549 cells. In conclusion, the present study demonstrated that miR‑145 regulates the EGFR/PI3K/AKT signaling pathway in patients with NSCLC.