Objective <p>Knee osteoarthritis (KOA), predominantly affecting middle-aged and elderly populations, induces localized joint pain and functional impairment. It was to evaluate the effectiveness of acupotomy bone decompression (ABD) combined with sodium hyaluronate (SH) intra-articular injection on inflammatory responses in treating KOA.</p> Methods <p>Clinical data from 128 patients with KOA were retrospectively collected, categorized into SH group (<i>n</i> = 55) and ABD + SH group (<i>n</i> = 73). Pain was assessed using the visual analogue scale (VAS), knee joint function was evaluated, and knee joint balance and gait parameters were measured. The status of articular cartilage and bone marrow edema was evaluated using quantitative magnetic resonance imaging (MRI). Interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, matrix metalloproteinase (MMP)-3, MMP-9, and hypersensitive C-reactive protein (hs-CRP) were detected.</p> Results <p>ABD + SH group showed drastic reductions in VAS scores, decreased indices of different axial balances, and increased stride length and walking speed versus the SH group (<i>P</i> &lt; 0.05). Quantitative MRI examination revealed that relative to the SH group, ABD + SH group exhibited increased thickness of articular cartilage and reduced area of bone marrow edema post-treatment (<i>P</i> &lt; 0.05). Post-treatment levels of hs-CRP, IL-6, IL-1β, TNF-α, MMP-3, and MMP-9 were markedly lower in the ABD + SH group versus SH group (<i>P</i> &lt; 0.05). Moreover, the clinical effective rate in the ABD + SH group was drastically superior to the SH group (95.9% vs. 78.2%, <i>P</i> &lt; 0.05).</p> Conclusion <p>Combining ABD with SH treatment for KOA effectively alleviates patient pain and inflammatory responses.</p>