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Objective: To investigate the protective and therapeutic role of ginseng against silicon dioxide nanoparticles (SiO2NPs)-induced toxicity in the lungs. Methods: Sixty male rats were divided into five groups (n = 12/group); group 1 was used as a control, group 2 received ginseng, group 3 was treated with SiO2NPs, and group 4 was pretreated with ginseng one week before SiO2NPs, while group 5 was given SiO2NPs one week before supplementation with ginseng. Animals were treated with both ginseng and SiO2NPs orally for five weeks. Real-time PCR was used to measure gene expression. Besides, DNA damage and cell cycle changes were determined by comet assay and flow cytometry, respectively. Histological study was also done to assess the effect of ginseng on SiO2NPs-induced toxicity. Results: SiO2NPs increased lipid peroxidation and decreased the activities of antioxidant enzymes. SiO2NPs induced apoptosis in lung tissues as revealed by upregulation of Bax and caspase 3 and downregulation of Bcl-2 as well as the induction of DNA damage. SiO2NPs also caused inflammation as indicated by upregulation of the inflammation-related genes [interleukin 1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), cyclooxygenase 2 (COX2), and transforming growth factor-beta 1 (TGFβ1)] as well as cell cycle arrest in the G0/G1 phase of lung cells. Moreover, histopathological examination proved the biochemical and molecular perturbations that occurred due to SiO2NPs toxicity. However, ginseng alleviated SiO2NPs-induced toxicity in rat lung. Conclusions: Ginseng has a potent preventive and therapeutic effect and could be used in the treatment of SiO2NPs-induced pulmonary toxicity.