Oxidativestress, a pathological condition, contributes to the pathophysiology of a number of diseases including carcinogenesis. Numerous studies pointed out the disturbed antioxidants status and accumulation of oxidative stress markers in the carcinogenesis. The present study analyzed the anticancer efficacy of chlorogenic acid-loaded chitosan nanoparticles by utilizing the oxidative stress biomarkers as an endpoint in mice with skin cancer developed by 7,12-dimethylbenz(a)anthracene (DMBA). Oxidative stress markers' (lipidperoxidation by-products and antioxidants) levels or activitieswere measured using colorimetric assays. While mice exposed with DMBA alone showed a 100% tumor incidence, 0 and 50% tumor formation was seen in mice treated with DMBA + topical application of the nanoparticles and DMBA + orally administered nanoparticles, respectively. Also, the study noticed a 33% and 67% tumor incidence in mice treated with DMBA + topical application of free chlorogenic acidand DMBA + orally administered free chlorogenic acid, respectively. The present study noticed that the topical application of chlorogenic acid-loaded chitosan nanoparticles to DMBA-painted mice completely suppressed the tumor growth and restored the levels or activities of oxidative stress markers as compared to mice that received DMBA + oral administration of chlorogenic acid-loaded chitosan nanoparticles. The study observed that chlorogenic acid-loaded chitosan nanoparticles are more potent than free chlorogenic acid in preventing skin cancer in mice caused by DMBA. Thus, the present investigation explores the tumor-inhibiting efficacy of chlorogenic acid-loaded chitosan nanoparticles in experimental skin cancer, and the tumor preventive efficiency could be attributed to their antilipid peroxidative and antioxidant effects.