ABSTRACT: Background:As a pathological process, osteonecrosis of the femoral head (ONFH) is characterized by the avascularity of the femoral head, cellular necrosis, microfracture, and the collapse of the articular surface. Currently, critical treatment for early-stage ONFH is limited to core decompression. However, the efficacy of core decompression remains controversial. To improve the core decompression efficacy, regenerative techniques such as the use of platelet-rich plasma (PRP) were proposed for early-stage ONFH. As a type of autologous plasma containing concentrations of platelets greater than the baseline, PRP plays an important role in tissue repair, regeneration, and the differentiation of mesenchymal stem cells (MSCs). In this review, we present a comprehensive overview of the operation modes, mechanism, and efficacy of PRP for early-stage ONFH treatment. Methods:We searched for relevant studies in the PubMed, Web of Science, and Embase databases. By searching these electronic databases, the identification of either clinical or experimental studies evaluating PRP, MSC, core decompression, and ONFH was our goal. Results:Seventeen studies of PRP and avascular necrosis of the femoral head were evaluated in our review. Ten studies related to the possible mechanism of PRP for treating ONFH were reviewed. Seven studies of the operation modes of PRP in treating ONFH were identified. We reviewed the efficacy of PRP in treating ONFH systematically and made an attempt to compare the PRP operation modes in 7 studies and other operation modes in past studies for early-stage ONFH treatment. Conclusion:PRP treats ONFH mainly through three mechanisms: inducing angiogenesis and osteogenesis to accelerate bone healing, inhibiting inflammatory reactions in necrotic lesions, and preventing apoptosis induced by glucocorticoids. In addition, as an adjunctive therapy for core decompression, the use of PRP is recommended to improve the treatment of early-stage ONFH patients, especially when combined with stem cells and bone grafts, by inducing osteogenic activity and stimulating the differentiation of stem cells in necrotic lesions.