Oxymatrine is one of the primary natural compounds extracted from the Sophora flavescens, and has been reported to exhibit numerous pharmacological properties including cancer‑preventive and anti‑cancer effects, however the mechanisms as to how oxymatrine exhibits anti‑proliferative activity in non‑small cell lung carcinoma cells remains uncertain. The present study aimed to explore the mechanism of its anti‑cancer effect, and whether it is due to apoptosis induction and anti‑migration in the A549 lung cancer cell line. Detection of morphological alterations, MTT analysis, Hoechst/propidium iodide dual staining and terminal deoxynucleotidyl transferase dUTP nick end labeling assays verified that oxymatrine induced A549 cell apoptosis. The caspase pan‑inhibitor z‑VAD‑FMK resulted in disappearance of oxymatrine‑elicited nuclei fragmentation via Hoechst 33342 staining. JC‑1 staining demonstrated a decrease in mitochondrial membrane potential which further verified the induction of apoptosis by oxymatrine. The caspase‑3, 8 and 9 activities of oxymatrine‑treated cells were activated, which suggested that extrinsic and intrinsic apoptotic pathways were involved in the anti‑proliferative effects of oxymatrine in A549 cells. Furthermore, the wound healing assay verified the anti‑migratory effects of oxymatrine in A549 cells.