Objective To investigate the clinical efficacy of platelet-rich plasma (PRP) in the treatment of knee osteoarthritis (KOA) and its potential engineering mechanism to promote the repair of articular cartilage in KOA. Methods A total of 80 patients with KOA who were admitted to the First Affiliated Hospital of Bengbu Medical University between June 2022 and April 2024 were randomly divided into two groups: a PRP group and a control group. Each group consisted of 40 patients who received different treatments. The PRP group received autologous PRP injections, while the control group received sodium hyaluronate injections. Both treatments were administered over a period of six weeks. The following were evaluated before treatment and at weeks 4, 8 and 12 post-treatment: clinical symptoms (VAS, WOMAC and Lysholm scores); Magnetic resonance imaging(MRI) structures (cartilage thickness, bone marrow oedema and synovial hyperplasia; WORMS scores); and levels of inflammatory factors (IL-1β, TNF-α and MMP-13) and signalling pathway-related proteins (NF-κB p65 and IKKβ). Results There was no statistically significant difference in baseline characteristics and baseline indicators between the two groups before treatment (All P>0.05). After treatment, the PRP group was significantly better than the control group in terms of pain relief and improvement in joint function (All P<0.05), and the MRI results showed a significant increase in cartilage thickness, a more significant improvement in BMLs and synovitis (P <0.05), and a greater decrease in WORMS scores. Molecular level analysis showed that IL-1β, TNF-α, MMP-13 levels and NF-κB pathway protein expression were significantly down-regulated in the PRP group compared with the pre-treatment period and were better than those in the control group (All P<0.05). Conclusion PRP can effectively relieve pain and improve joint function in patients with KOA, promoting cartilage structural repair by inhibiting the expression of inflammatory factors and the activation of the NF-κB signalling pathway. It is effective, safe and has high clinical value. This study also provides a multimodal engineering research perspective on PRP for repairing articular cartilage.