Objective To analyze the correlation between serum levels of C-X-C motif chemokine 5(CXCL5),Toll-like receptor 4(TLR4),and matrix metalloproteinase-3(MMP-3)with the degree of joint destruction and serum uric acid(SUA)levels in gouty arthritis patients with different clinical characteristics,and to evaluate their predictive value for severe GA.Methods A total of 212 GA patients(GA group)diagnosed at Xi'an People's Hospital between June 2023 and June 2025 were enrolled,along with 212 healthy individuals(control group).Predictive value was assessed using receiver operating characteristic(ROC)curve analysis,and correlation was assessed using Pearson method.Results Serum levels of CXCL5,TLR4,and MMP-3 were significantly higher in the GA group compared to the control group(P<0.05).Statistically significant differences in serum levels of CXCL5,TLR4,and MMP-3 were observed among GA patients with different clinical stages,affected joints,presence of tophi,disease duration,and annual attack frequency(P<0.05).The severe GA group had higher levels of CXCL5,TLR4,and MMP-3 compared to the mild GA group(P<0.05).GA patients were at higher risk for severe disease when serum CXCL5,TLR4,and MMP-3 levels exceeded 612.56 pg/mL,11.15 ng/mL,and 12.06 ng/mL,respectively.The combined prediction of severe GA by CXCL5,TLR4,and MMP-3 yielded an area under the curve(AUC)of 0.963.Compared to low-expression patients,those with high expression of CXCL5,TLR4,and MMP-3 had a 2.758-fold,2.184-fold,and 2.227-fold increased risk of severe GA,respectively.CXCL5,TLR4,and MMP-3 were identified as influencing factors for the disease severity(P<0.05).The high SUA group had significantly higher serum levels of CXCL5,TLR4,and MMP-3 compared to the low SUA group(P<0.05).Conclusion GA patients exhibit high serum expression of CXCL5,TLR4,and MMP-3,which are significantly associated with clinical features,the degree of joint destruction,and SUA levels,demonstrating considerable clinical value.