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• Complement system proteins and their regulators promote tumor growth. • Its activation is an important prerequisite for role in tumor growth and anti-tumor response. • Its contradictory role in cancer might be a very crucial factor for the positive outcomes of immunotherapies. • Complement resistance not only influences the course of disease but also the patients' prognosis. Complement system proteins, their regulators and endpoint effector complex significantly promote tumor growth by upregulation of oncogenic growth factors, activation of mitogenic signalling pathways and breakage of normal cell cycle. Contrastingly, complement cascades, initiated by anti-tumor therapeutic antibodies, also play a pivotal role in therapy response. This contradictory role of complement system possibly be a very crucial factor for the outcomes of antibody mediated immunotherapies. Herein, we reviewed the twin role of the complement system in cancer and also the genetic variations in complement system genes. Future studies should be focused on the biomarker discovery for the personalised cancer immunotherapies. [ABSTRACT FROM AUTHOR]