In recent years, the development of approaches to treatment of malignant neoplasms based on the use of biomolecules such as proteins that are able to selectively kill tumor cells without causing undesired side effects has become increasingly urgent. The use of specially designed antibodies against antigens that are specific for tumor cells can be classified as one of these approaches. These antibodies are able to suppress tumor cells either as a result of blocking the receptors needed to maintain their viability, or by the action of a toxin that is covalently coupled to the antitumor antibody. Another group of protein molecules that have no less therapeutic potential is oncotoxic proteins, i.e., molecules that, when entering tumor cells, trigger a cascade of proapoptotic signals that depend on pathological signaling pathways specific to transformed cells. Systems of the activated proliferation, dysregulation of the cell cycle, the induction of apoptosis, mitochondrial respiration, and glycolysis activation can be the targets for oncolytic proteins in tumor cells. The application of oncotoxic proteins can significantly add to the arsenal of antitumor agents.