Objective: To explore the relationship between mechanical parameters of meniscus protrusion, inflammatory factors in knee joint effusion and knee cartilage degeneration. Methods: A total of 60 patients with meniscus protrusion and cartilage degeneration (degeneration group) and 60 patients only with meniscus protrusion (control group) in the hospital were enrolled. The displacement of meniscus protrusion and width of joint space were quantified by MRI. The levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-3 (MMP-3) in knee joint effusion were detected by enzyme-linked immunosorbent assay. The influencing factors of cartilage degeneration were analyzed by Logistic regression analysis, and their predictive value in cartilage degeneration was evaluated by receiver operating characteristic (ROC) curves. Results: The average length of meniscus protrusion, width of joint space, levels of IL-1β, TNF-α and MMP-3 in knee joint effusion in degeneration group were higher than those in control group (P<0.05). Logistic regression analysis showed that the increased protrusion displacement and IL-1β were independent predictors of cartilage degeneration (P<0.05). ROC curves analysis showed that area under the curve (AUC) and sensitivity of increased displacement of meniscus protrusion and IL-1β for predicting cartilage degeneration respectively were (0.869, 0.821) and (88.33%, 83.33%), respectively. The AUC for predicting cartilage degeneration with the combination of the two was 0.909, with a sensitivity of 90.00%, indicating good predictive performance (P<0.05). Conclusion: The increased displacement of meniscus protrusion and IL-1β in knee joint effusion are important early warning indexes of knee cartilage degeneration. The combined detection is of significant clinical value for the early identification of high-risk patients.