Lung cancer, a leading cause of cancer‑related deaths, is frequently diagnosed in both males and females worldwide. In the present study, the Ras homologue GTPase activation protein 6 (ARHGAP6), which belongs to the Rho GTPase‑activating protein (RhoGAP) family, was found to have low expression in tumor tissues from patients with lung cancer, accompanied by high expression of matrix metalloproteinase‑9 (MMP9) and vascular endothelial growth factor (VEGF). In A549 and H1299 cells, upregulation of ARHGAP6 inhibited tumor growth and metastasis and reduced the levels of MMP9, VEGF and p‑STAT3, while the levels STAT3 were unchanged, as demonstrated by CCK‑8, migration and invasion assays as well as western blot analysis. In addition, interleukin 6 (IL‑6)‑induced migration, invasion and MMP9 and VEGF expression, and STAT3 signaling activity were suppressed by ARHGAP6 upregulation. Based on these data, we concluded that ARHGAP6 is critically important in lung cancer progression and that upregulation of ARHGAP6 benefits the treatment and prevention of lung cancer, possibly through the suppression of MMP9, VEGF and STAT3 signaling activation.