Background: Fucoxanthin (Fx), an distinctive carotenoid occurs on brown seaweed, contains several benefits including anti-cancer effects. To investigate the chemopreventive effectual of Fx on 7,12-dimethylbenz[a] anthracene (DMBA)-alone skin tumor development in Swiss albino mice. Materials and Methods: The skin sarcoma being provoked on the hairless flipside of the mice's skin, twice weekly for 8 weeks through challenging through DMBA (25 μg on 0.1 ml acetone/mice). Thereafter, the mice were oral supplementation with 50 mg/kg body weight (BW), Fx for 25th week a frequency of three times/week. Tumor size, change in BW, the cumulative quality of papillomas and some oxidative stress-related parameters were measured. Results: Orally administered Fx were notably increased BW, delayed tumor incidence with no abnormal pathology in DMBA-induced skin tumor mice. Fx effectively modulates the level of xenobiotic enzymes, brought back to the statuses of lipid peroxidation (LPO) enzymes and increased antioxidant enzymes status in squamous cell carcinomas (SCC). A considerable decrease in the protein expression of proinflammatory markers that is interleukin (IL) 1-6, tumor necrosis factor-alpha (TNF-α), and IL-β and restored the expression status of inflammatory regulators such as nuclear factor-kappa B (NF-κB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) on serum. These findings were supported through histopathological examinations. Hence, it was clear that Fx possessed a good anticancer activity against skin cancer. Conclusion: The chemopreventive prospective of Fx was eventually owing to its altering capacity on the levels of proinflammatory (IL 1-6, TNF-α, and IL-β) cytokines, inflammatory (NF-κB, COX-2, and iNOS) markers, LPO, antioxidants, and toxin-eliminating mediators in DMBA-provoked skin SCC. Thus, it can be concluded that the FX indicates the antitumor potential on DMBA challenged skin tumor proliferation model on mice.