Cancer is one of the leading causes of mortality worldwide. The present study was carried out to evaluate the anti-cancer activity of methanolic extract of Lagenaria siceraria on skin Papilloma model in mice. Lagnaria sciceria leaves and fruit extract against 7, 12 - dimethylbenz (a) anthracene (DMBA) induced papillomagenesis in Swiss albino mice was studied. The methanolic extract of Lagnaria sciceraria was analyzed for chemopreventive activity. It was evaluated by two stage protocol consisting of initiation with a single topical application of a carcinogen (7, 12 - dimethylbenz (a) anthracene (DMBA) followed by a promoter (croton oil) two times in a week were employed. A significant reduction in tumor incidence, tumor burden and cumulative number of papillomas was observed, along with a significant increase in average latent period in mice treated topically with Lagnaria sciceraria extract as compared to the control group treated with DMBA and croton oil. The Phytochemical analysis of methanolic extract of leaves and fruits of Lagnaria sciceraria showed presence of Alkaloids, triterponoids, flavonoids steroid, glycoside, tannin resin and saponin. However in methanolic extract of fruits of Lagnaria shows presence of all above compounds except alkaloids. The carbohydrate and protein were present in fruit extract which were absent in leaves sample. The above studies revealed information about the anticancer activity of Lagnaria sciceraria extracts.