Sodium Danshensu, extracted from the root of the Salvia miltiorrhiza, has pleiotropic effects including anti‐oxidation, anti‐inflammation and anti‐tumor. However, whether Sodium Danshensu has an anti‐cancer effect in lung cancer remains to be elucidated. The present study aimed to illustrate the effects of Sodium Danshensu on lung cancer cells and the potential molecular mechanisms. BEAS‐2B, A549, and NCI‐H1299 cells were stimulated with 25, 50, and 100 μM Sodium Danshensu for 24, 48, and 72 h, and then cell viability, apoptosis, migration and invasion were determined using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT), flow cytometry and Transwell assays, respectively. Moreover, the levels of Proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 9 (MMP9), B‐cell lymphoma‐2 (Bcl‐2) associated X (Bax), Bcl‐2, phosphorylated (p)‐phosphoinositide 3‐kinase (PI3K), and p‐Protein kinase B (AKT) in lung cancer cells were evaluated using quantitative real‐time polymerase chain reaction (qRT‐PCR) and/or Western blot assays. We observed that Sodium Danshensu suppressed cells viability, migration, and invasion, as well as promoted cells apoptosis in A549 and NCI‐H1299 cells in a dose‐dependent manner, while Sodium Danshensu had no cytotoxic effect on the proliferation activity of BEAS‐2B cells. Moreover, the expression of PCNA, MMP9, Bcl‐2 were decreased, but Bax was up‐regulated in Sodium Danshensu‐treated A549 and NCI‐H1299 cells. Our findings also revealed that Sodium Danshensu inhibited PI3K/AKT pathway in A549 and NCI‐H1299 cells. In conclusion, our study provided the first evidence that Sodium Danshensu suppressed the malignant biological behaviors of lung cancer cells, indicating that Sodium Danshensu might be a latent candidate for lung cancer therapy.