Objectives: Intra-articular application of platelet-rich plasma (PRP) are found to effectively improve knee function in patients with Knee osteoarthritis (KOA). This study is to identify the factors that influence the effect of PRP in the treatment of KOA. Methods: PRP was performed with a rich-leukocyte autologous conditioned plasma (ACP) system in 82 patients who were diagnosed with KOA. A Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used to score the level of KOA by 3 features as the evaluation indicator of therapeutic effect. Visual Analogue Scale (VAS), X-ray and subsequent Kellgren-Lawrence (K-L) scale level evaluation were performed before the treatment. Basic information of participants and disease duration were also collected. Simple correlation analysis, single-factor ANOVA and multivariant regression analysis were used for identifying factors associated with the efficiency of PRP injection. Results: WOMAC decreased after PRP therapy by 10.12 ± 0.98 points (P < 0.001). Simple correlation analysis and ANOVA suggest BMI, pre-treatment VAS scores, and pre-treatment K-L scale level positively correlated with the therapeutic effect of PRP treatment (P < 0.05), while the other factors were not significantly correlated with the effect (P > 0.05). Further multivariate model indicates that the responsible variable Y (Post-treatment changes of WOMAC scores) was affected by exploratory variables BMI (X1), VAS (X2), K-L scale level (X3) and Gender (X4) (F = 7.857, P < 0.001). The exploratory variable X3 had the biggest effect on Y.Conclusion: This study found that the therapeutic effect of PRP is better in male patients with higher BMI, higher VAS and lower K-L scale level.This study was qualified and registered in the Chinese Clinical Trial Registry as ChiCTR2000039856.