Proteins, a type of natural biopolymer that possess many prominent merits, have been widely utilized to engineer nanomedicine for fighting against cancer. Motivated by their ever-increasing attention in the scientific community, this review aims to provide a comprehensive showcase on the current landscape of protein-based nanomedicine for cancer therapy. On the basis of role differences of proteins in nanomedicine, protein-based nanomedicine engineered with protein therapeutics, protein carriers, enzymes, and composite proteins is introduced. The cancer therapeutic benefits of the protein-based nanomedicine are also discussed, including small-molecular therapeutics-mediated therapy, macromolecular therapeutics-mediated therapy, radiation-mediated therapy, reactive oxygen species-mediated therapy, and thermal effect-mediated therapy. Lastly, future developments and potential challenges of protein-based nanomedicine are elucidated toward clinical translation. It is believed that protein-based nanomedicine will play a vital role in the battle against cancer. We hope that this review will inspire extensive research interests from diverse disciplines to further push the developments of protein-based nanomedicine in the biomedical frontier, contributing to ever-greater medical advances.