The accumulation of fibrin/fibrinogen and other coagulation factors in and around solid tumors and metastatic foci has been recognized for a century as an aspect of cancer pathology. On this basis, anticoagulants and fibrinolytic agents have been deployed as adjuvant anticancer therapies, but they have proved clinically useful for only a small proportion of tumors and they only control the functions of the coagulant components. Overuse or long-term application of anticoagulants and fibrinolytic agents often lead to undesirable side-effects. Here, we propose that anticancer drugs that act by different mechanisms can inhibit tumor-associated coagulation, and it may be possible to develop drugs that specifically targeting tumor-related coagulation, have specific cytotoxic effects on tumor and metastatic cells. We provide laboratory and clinical evidence supporting the hypothesis and offer proposals for future applications.