Abstract:[Objective] To explore the clinical efficacy and possible mechanism of arthroscopic debridement combined with platelet rich plasma (PRP) in the treatment of mild-to-moderate knee osteoarthritis (KOA). [Methods] A total of 110 patients with mild to moderate KOA admitted from January 2021 to April 2022 were randomly divided into two groups, with 55 patients in each group. The combined group received arthroscopic debridement combined with PRP, while the debridement group received arthroscopic debridement only. The documents regarding perioperative period, follow-up and auxiliary examination were compared between the two groups. [Results] There were no significant differences in operation time, total incision length, intraoperative blood loss, walking time, incision healing grade and hospital stay between the two groups (P>0.05), while the combined group proved significantly superior to the debridement in term of the swelling VAS score 7 days postoperatively [(4.0±1.1) vs (4.5±1.0), P<0.05]. The follow-up period lasted for more than 12 months, and the combined group resumed full weight-bearing activity significantly earlier than the debridement group [(45.2±6.2) days vs (50.1±7.2) days, P<0.05]. The VAS, WOMAC and Lysholm scores were significantly improved over time in both groups (P<0.05). The combined group proved significantly better than the debridement group in terms of VAS [(1.3±0.4) vs (2.1± 0.6), P<0.05], WOMAC [(25.0±5.2) vs (31.5± 5.0), P<0.05] and Lysholm scores [(90.5±8.0) vs (85.3±8.1), P<0.05]. Regarding auxiliary examination, the serum levels of TLR-4, MMP-9 and SDF-1 in both groups were significantly decreased 1 month after treatment compared with those before treatment (P<0.05). The combined group was significantly lower than the debridement group in TLR-4 [(7.0±2.0) ng/ml vs (8.4±2.2 ng/ml, P<0.05], MMP- 9 [(26.0±7.0) pg/ml vs (30.1±7.3) pg/ml, P<0.05] and SDF-1 [(453.4±47.2) μg/L vs (495.8±52.2) μg /L, P<0.05]. [Conclusion] The arthroscopic debridement combined with PRP does relieve pain and improve knee joint function for mid and moderate KOA, its mechanism may be related to reducing blood TLR-4, MMP-9 and SDF-1 levels.