Cancer is the leading cause of death worldwide and current mode of cancer treatment causes side effects on normal cells and are still the key challenges in cancer treatment. However, natural products or active compound of medicinal plants are being safe, affordable, and effective in diseases cure.In this context, scientific studies evidence the health promoting effects of natural products, which work through its anti-oxidant, anti-inflammatory and anti-cancer activity. Thymoquinone (TM), a predominant active compound of Nigella sativa, has confirmed antineoplastic activity through its ability to regulate various genetic pathways. In addition, thymoquinone has established anti-cancerous effects through killing of various cancerous cells, inhibit the initiation, migration, invasion and progression of the cancer. The anti-cancer effects of TM are chiefly mediated via regulating various cell signaling pathways such as VEGF, bcl2/bax ratio, p53, NF-kB and oncogenes.The anti-cancer drugs have limitations in efficacy and also causes adverse side effects on normal cells. The combination of anti-cancer drugs and thymoquinone improve the efficacy of drugs as evidences by decrease resistance to drugs and regulating various cell signaling pathways. Moreover, combination of anti-cancer drugs as well as thymoquinone shows synergistic effect on killing of cancer cells and cells viability. Thus TM in combination with anti-cancer drugs can be a good strategy in the management of various types of cancer.In this review article, we deliver an outline of thymoquinone role in cancer inhibition and prevention of cancer based on in vivo and in vitro studies. Further studies on thymoquinone based on clinical trials are highly required to explore the benefits of thymoquinone in cancer management.