Placenta-specific protein 1 (PLAC1) is an important member of the cancer-testis antigens (CTA) family, which exhibits tumor-specific expression patterns. It is abnormally highly expressed in multiple malignant tumors, while it is only found in the testis and placenta in normal tissues. It has been discovered that PLAC1 is involved in the process of tumor occurrence and development and has become a potential diagnostic marker and therapeutic target. PLAC1 also exhibits significant carcinogenicity in head and neck squamous cell carcinoma (HNSCC). Based on its high immunogenicity and tumor specificity, antibody-coupled drugs and peptide vaccines of targeting PLAC1, and other therapies are currently under development. Nano-targeting technology also shows potential for cross-species cancer treatment. This paper summarized the structural characteristics, expression patterns, and regulation mechanisms of PLAC1 expression, as well as its role in tumor occurrence and development. The paper also reviewed its biological function and therapeutic prospects in HNSCC.