Objective Screening the differentially expressed proteins related to apoptosis in cold-dampness syndrome of rheumatoid arthritis (RA). Methods Peripheral blood mononuclear cells (PBMCs) were collected from healthy people and RA patients with cold-dampness syndrome. 43 apoptosis-related proteins were detected by antibody chip, which was verified by ELISA. Results In 43 apoptosis-related proteins, 10 of them were up-regulated and 3 were down-regulated. The most differentially expressed were tumor necrosis factor receptor 5 (CD40) and soluble tumor necrosis factor receptor 2 (sTNFR2). Compared with the normal group, the expression of CD40 and sTNFR2 in RA patients with cold-dampness syndrome increased significantly. The results of receiver operating characteristic curve (ROC) showed that CD40(AUC=0.8133) and sTNFR2(AUC=0.8117) could be used as diagnostic markers of RA patients with cold-dampness syndrome. The results of Spearman correlation analysis showed that CD40 was negatively correlated with Fas and Fas ligand (FasL), while sTNFR2 was positively correlated with erythrocyte sedimentation rate and negatively correlated with mental health score (MH). Logistic regression analysis showed that rheumatoid factor (RF), 28 joint disease activity scores (DAS28) and vitality (VT) were risk factors for CD40. ESR, anti-cyclic citrullinated peptide (CCP) antibody, self-rating depression scale (SAS) and MH were the risk factors of sTNFR2. Conclusion CD40 and sTNFR2 are proteins related to apoptosis in RA patients with cold-dampness syndrome, which are closely related to clinical indexes and apoptosis indexes.