Cancer is one of the deadliest diseases, continually prompting physicians and researchers to investigate safe and effective modalities for its treatment. Piezoelectric nanomaterial is a new class of material with enormous potential for the nanoscale and bidirectional conversion of mechanical strain into electric fields for cancer treatment. In response to ultrasound mechanical strain, a piezopotential and electric field is generated in the tumor microenvironment, which reduces the growth of cancer cells by catalyzing redox reactions and the synthesis of reactive oxygen species. In this review, we discuss the basic concepts and mechanisms of biopiezoelectric nanomaterials as anti-cancer agents. We provide a comprehensive summary of current state-of-the-art piezoelectric nanoparticles as anti-cancer therapies. Lastly, we identify current challenges that must be addressed for the proper clinical development of biopiezoelectric nanomaterial-based anti-cancer agents and provide future perspectives for the development of this technology.