In many developed countries, colorectal cancer is a leading cause of morbidity and mortality and its etiology is familiar to be a grouping of nutritional and environmental factors, less physical activity and hereditary factors. Lycoperoside H (LH) is a steroidal alkaloid saponin commonly found in the tomato and exhibited the various pharmacological effects. The aim of the current study was to scrutinized the anticancer effect of LH against 1,2âDimethyl Hydrazine (DMH) induced colorectal cancer (CRC) in rats. Subcutaneous injection of DMH (20 mg/kg) was used for induction the CRC and rats were received the oral administration of LH (10, 20 and 40 mg/kg) for 16 weeks. At the end of the investigation, the tumor incidence, weight, and body weight were calculated. Antioxidant enzymes (phase I and II), inflammatory cytokines, lipids and inflammatory markers were all examined. DMH induced rats exhibited the increased tumor incidence, reduced body weight and LH treatment significantly (p < 0.001) suppressed the tumor incidence, and enhanced the body weight. LH treatment significantly (p < 0.001) boosted the level of SOD, GPx, GSH, CAT and suppressed the MDA level. LH treatment suppressed the level cytochrome b5 (Cyto b5), cytochrome P450 (Cyto P450) and boosted the level of glutathione Sâtransferase (GST), uridine diphosphoglucuronyltransferase (UDPâGT) in the liver and colon tissue. LH also decreased the level of cytokines includes interleukin-6 (IL-6), interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha); inflammatory mediators like Inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), prostaglandin (PGE2) and nuclear factor kappa B (NF-kappaB) in the hepatic and colon tissue. We can conclude that LH revealed the anticancer effect against the DMH induced CRC via suppression of inflammation and oxidative stress.