Objective To investigate the clinical effect of platelet-rich plasma(PRP) combined with core decompression in the treatment of early spontaneous osteonecrosis of the knee(SONK). Methods A retrospective analysis of SONK patients with Koshino stage I and Ⅱ admitted to our hospital from June 2015 to June 2020 was carried out. According to the different treatment methods, patients were divided into core decompression group (control group, 21 patients), and knee joint cavity PRP injection combined with core decompression group (PRP group, 22 patients). The VAS scores and WOMAC scores before treatment, 1, 3, 6 and 12 months after surgery were compared between the two groups to assess the knee joint function, and observed whether there were complications. Results Forty-three patients were followed up for 12 to 62 months after the operation. After treatment, the two groups had no complications such as wound infection, joint infection, or deep vein thrombosis. The preoperative VAS score and WOMAC score of the two groups were not significantly different (P>0.05);compared with those before the operation, VAS score and WOMAC score were significantly different at 1, 3, 6, and 12 months after the operation (P<0.05); compared with the control group, the VAS score of the PRP group was significantly reduced at 3, 6, and 12 months after surgery (P<0.05), and the WOMAC score of the PRP group was significantly improved at 6 and 12 months after surgery (P<0.05). The overall effective rates of the PRP group and the control group were 90.48% (19/21) and 77.27% (17/22) respectively, and the difference between the two groups was statistically significant (P<0.05). In the follow-up 12 months after the completion of the treatment, 6 patients in the control group and 2 patients in the PRP group underwent unicondylar replacement. Conclusion The combination of platelet-rich plasma and core decompression in the treatment of early SONK was safe and effective, and the clinical effect was better than that of core decompression only.