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Doxorubicin (DOX) constitutes the major constituent of anti-cancer treatment regimens currently in clinical use. However, the precise mechanisms of DOX’s action are not fully understood. Emerging evidence points to the pleiotropic anticancer activity of DOX, including its contribution to DNA damage, reactive oxygen species (ROS) production, apoptosis, senescence, autophagy, ferroptosis, and pyroptosis induction, as well as its immunomodulatory role. This review aims to collect information on the anticancer mechanisms of DOX as well as its influence on anti-tumor immune response, providing a rationale behind the importance of DOX in modern cancer therapy.