Silymarin, the active extract from milk thistle, has been extensively used in patients with liver disease of different etiology. Although silymarin is a complex of 7 flavonolignans and polyphenols, silibinin is usually regarded as the most active component. In vitro and in vivo studies indicate that silymarin and silibinin protect the liver from oxidative stress and sustained inflammatory processes, mainly driven by Reactive Oxygen Species (ROS) and secondary cytokines. Oxidative stress and inflammation are also involved in cellular damage of many other tissues and their role in the development and toxic reactions in patients receiving cancer therapies is established. The protective effects of silymarin and silibinin, demonstrated in various tissues, suggest a clinical application in cancer patients as an adjunct to established therapies, to prevent or reduce their toxicity. Here we discuss the possible mechanism of the protective action of silymarin and silibinin, focusing on cancer therapies as agents causing cellular damage.