AbstractAimImpaired apoptosis and proliferation resulted in autoreactive lymphocyte development and inflammation in Rheumatoid arthritis (RA).TP53,BAX,FOXO1, andRB1are related genes in cell survival, proliferation, and inflammation which could be important in RA development and disease severity. Here we investigated their expression in peripheral blood mononuclear cells (PBMCs) from RA patients in comparison to healthy controls.MethodsFifty healthy controls and 50 RA patients were selected. The quantitative real‐time polymerase chain reaction was used to assess the gene expression level in PBMCs.ResultsThe mRNA expression ofTP53(FC = 0.65,p= .000),BAX(FC = 0.76,p= .008),FOXO1(FC = 0.59,p= .000) andRB1(FC = 0.50,p= .000) were significantly reduced in RA PBMCs.TP53expression was negatively correlated with miR‐16‐5p (p= .032) andFOXO1expression was negatively correlated with miR‐335‐5p (p= .005) and miR‐34a‐5p (p= .014). A positive correlation was seen betweenTP53expression and its downstream gene,BAX(p= .001).FOXO1expression was also negatively correlated with disease activity, DAS28 (p= .021).ConclusionAll selected genes have downregulated expression in RA PBMCs which could be correlated with RA pathogenesis by regulating apoptosis, cell survival, inflammatory mediator production, and proliferation. Due to the correlation of miR‐16‐5p, miR‐34a‐5p, and miR‐335‐5p withTP53andFOXO1expression in RA PBMCs, they could be used as future therapeutic targets.