Lung cancer is recognized as the most prevalent type of cancer with high death rate. Ginsenoside Rg3 isolated from Traditional Chinese Medicine Panax Ginseng has significant anticancer effects on many tumors. In this study, the effects of ginsenoside Rg3 on cells viability, apoptosis and PI3K/Akt signaling pathway in lung cancer cells were investigated in vitro and in vivo. In vitro, the viability of lung cancer cell lines A549，H23 was examined by CCK-8 kits; The proportion of cell apoptosis was measured by flow cytometry. The expression of p-PI3K/PI3K and p-Akt/Akt was evaluated with Western blot. In vivo, A549，H23 cells were subcutaneously injected into the nude mice. Histopathological analysis was stained with HE, and TUNEL assay was used to detect cell apoptosis. The results showed that Rg3 obviously inhibited cell viability, induced apoptosis and inhibited PI3K/Akt signalling pathway on A549, H23 cells in vitro and in vivo. Rg3 effectively inhibited the volume and weight of tumor in xenografts model, which may be related with inhibiting PI3K/Akt signaling pathways.