Nicotine-derived nitrosamine ketone (NNK) is considered a key tobacco smoke carcinogen inducing lungtumors. Physalis peruviana L (harankash) is considered one plant with marked health benefits. This studyaimed to evaluate Physalis peruviana L effect on the toxic effect of NNK induced lung cancer in the rats by usingpulmonary histopathological, immunohistochemical and DNA flow cytometric analyses. Sixty adult male ratswere divided into four groups, each consisting of fifteen animals. The first group received saline, the secondreceived two successive toxic doses of NNK only while the third received two successive toxic doses of NNK witha single daily dose of Physalis peruviana L. The fourth group received a single daily dose of Physalis peruviana Lonly. Toxic doses of NNK induced hyperplasia and adenocarcinoma in the lung and positive immunoreactivityfor Ki-67 and p53 staining with disturbance of the lung DNA content. Administration of Physalis peruviana Lwith NNK led to a mild pulmonary hyperplasia and weak expression of Ki-67 and p53 with an improvementin the lung DNA content. Physalis peruviana L may protect against NNK induced lung carcinogenesis due to itsantioxidant and anti-proliferative effects.