Toxic heavy metals such as cadmium and arsenic are considered as the important factors contribute to the development and progression of various types of cancers such as colorectal cancer (CRC). These elements induce toxicity and mutagenesis through interference with metabolic intracellular activity and generation of oxidative stress and inflammation, by production of reactive oxygen species (ROS), reactive nitrogen species (RNS) and cyclooxygenase 2 (COX 2). Anti-oxidant agents such as Black Cumin (Nigella sativa L.) as a traditional medicinal plant could modulate toxicity of heavy metals. This review discusses the mechanisms of Black cumin actions in the modulation of inflammation and oxidative stress in CRC. Relevant studies in electronic databases were selected by searching MEDLINE Library. Only relevant English published articles were included. Available evidence reported that production of inflammatory mediators such as ROS, NOS and COX2, stimulated by toxic heavy metal, are associated with tumor progression and destruction of biological macromolecules such as DNA, proteins and lipids in sensitive signaling pathways of cells. However, existing evidence proposed that, Black cumin or extracted phenolic components of that could modulate inflammation and oxidative stress in CRC through following mechanisms. 1) decreasing the ROS, nitrite and inducible nitric oxide synthase production from neutrophils; 2) scavenging the produced ROS and nitric oxide; 3) decreasing the activation and emigration of neutrophils; 4) enhancement the levels of antioxidant enzymes like glutathione peroxidase and superoxide dismutase; 5) inhibiting the activation of NF-kB and pro-inflammatory pathways; and 6) inhibition of COX-2 pathway. Suppression of oxidative stress and inflammation might protect cells from destruction and tumor progression. Bioactive components of Black Cumin affect production of inflammatory mediators and oxidative stress and attenuate toxicities and tumorigenesis induced by inflammation and oxidative stress.