In cancer patients undergoing surgery, tumor biology and anticancer treatments can increase the risk of perioperative bleeding and blood transfusions. Notably, blood transfusions can be potentially associated with an increased risk of life-threatening immune responses, acute lung injury, postoperative infections, and thromboembolism. Moreover, the link between perioperative transfusion and increased risk of cancer recurrence cannot be excluded. On the other hand, cancer patients have an increased risk of thromboembolism due to cancer itself and antineoplastic systemic treatments including chemotherapy and anti-angiogenic drugs. In this complex scenario, effective and safe strategies aimed at the prevention of blood transfusions are warranted. This narrative review addresses the efficacy, and the safety of the synthetic antifibrinolytic agent tranexamic acid (TXA) when used perioperatively in cancer surgery. Although in not oncologic surgery the use of TXA has been extensively studied, in the setting of cancer patients requiring surgery, the evidence is scarce. An overview of the ongoing clinical research is also provided.