Photodynamic therapy (PDT) involves the administration of a photosensitizer followed by light irradiation with a specific wavelength, giving rise to irreversible tissue destruction. Hypericin, a herbal extract derived from Hypericum perforatum or St. John's Wort, has minimal toxicity but exhibits potent photo-damaging effects in the presence of light. Hypericin is known to generate a high yield of singlet oxygen and other reactive oxygen species that are associated with photo-oxidative cellular damage. The application of PDT with hypericin for the treatment of cancers such as recurrent mesothelioma and skin cancer has been validated in clinical trials. This mini-review focuses on the investigative studies of hypericin as a potential photodynamic agent in the treatment of nasopharyngeal cancer (NPC) in in vitro and in vivo models. NPC is an enigmatic tumor with a multifactorial etiology and a high incidence in the populations of Southern China.