Background: Milk thistle (Silybum marianum) has been traditionally used in medicine, particularly in the treatment of liver diseases. Today, it is used for the same purpose in evidence-based medicine (EBM). Its main active ingredient is a complex of flavonolignans, known as silymarin. Silymarin is used as a hepatoprotective agent, but its potential therapeutic use in oncology patients has drawn attention only recently. Purpose: The aim of this review is to provide comprehensive information on the potential therapeutic effects of milk thistle in oncology patients and potential indications for its use as a supportive therapy either as an anticarcinogenic agent or as an agent that attenuates the side effects of oncological treatments. Evidence of its effects and its safety, and possible interactions with other cancer treatments are emphasized. Available findings are supported mainly by in vitro studies and the results of animal research, but the number of clinical trials in oncology patients is increasing. Based on the results of these studies, milk thistle or silymarin could be beneficial in oncology patients, especially for the treatment of the side effects of anticancer chemotherapeutics. Evidence from clinical studies shows that it has mainly beneficial effects in hepatotoxicity and radiotherapy-induced skin and mucosa damage at dosages of 160–600 mg daily.