Rheumatoid arthritis (RA) is a chronic, progressive, systemic inflammatory disease with a global prevalence of 0.2 to 1.1%. The caspase-5 (CASP5) gene, part of the caspase family, plays a crucial role in apoptosis and immune response. The association between CASP5 expression gene levels in B cells and T cells PBMCs and CASP5 plasma level suggests that CASP5 could be a novel risk biomarker for RA. A case control study involving 80 subjects found that 15.0% of RA cases had mild activity, 30.0% had moderate activity, and 55.0% had high activity. RA cases were significantly associated with higher ESR and lower Hb compared to the control group. CASP5 plasma levels and CASP5 gene expression levels showed higher sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy compared to CASP5 plasma levels. Logistic regression analysis was conducted to predict RA susceptibility, finding that CASP5 plasma level and CASP5 gene expression level were both significantly linked with RA susceptibility