Protothecosis is a rare infection caused by members of genus Prototheca, which are opportunistic pathogens. Given the increasing number of immunocompromised individuals throughout the world, the incidence of protothecosis keeps increasing. The most common clinical manifestation of protothecosis is cutaneous protothecosis, as well as olecranon bursitis, fibrous tissue infection, and systemic infection. Because of the limited cases of protothecosis, the pathogenesis of protothecosis is largely unknown; the manifestations are lack of specificity; and it is commonly misidentified as the yeast in clinical laboratory. In order to improve the understanding of protothecosis, this paper reviews reported cases of protothecosis at home and abroad, and summarizes its etiology, pathogenesis, clinical manifestation, diagnostic features, treatment, and prognosis.