〔Abstract〕 Objective To investigate the expression of genes and proteins in the peripheral blood mononuclear cell(PBMC) cystine/glutamate antiporter system(System Xc-)/glutathione(GSH)/glutathione peroxidase 4(GPX4) ferroptosis pathway and its influence on inflammatory factors in patients with rheumatoid arthritis(RA). Methods 30 patients with RA and 30 healthy participants were enrolled. PBMCs were isolated using Ficoll-hypaque density gradient centrifugation. The cells were categorized into the healthy control, RA, ferroptosis inhibitor, ferroptosis inducer group. The cell viability was checked using the cell counting kit-8(CCK-8) method. Intracellular Fe2+relative fluorescence intensity and reactive oxygen species(ROS) levels were detected using the FerroOrange and Dihydroethidium(DHE) fluorescent probes, respectively. Western blot and real-time quantitative PCR(qPCR) detected the expression of nuclear factor erythroid 2-related factor 2(Nrf2), solute carrier family 7 member 11(SLC7A11), GPX4 proteins and mRNA. And the flow cytometry quantified the levels of tumor necrosis factor α(TNF-α), Interleukin(IL)-1, and IL-6 in the supernatant of each cell group. Results Compared to the healthy control group, the RA group showed a significantly increased Fe2+concentration and elevated ROS levels, reduced expression of Nrf2, SLC7A11 and GPX4 proteins and mRNA, and increased contents of TNF-α, IL-1 and IL-6 in PBMC supernatant, and the differences were statistically significant. The concentration of Fe2+and ROS levels in the inhibitor group were lower than those in the RA group, the proteins expressions of Nrf2, SLC7A11 and GPX4 increased, the mRNA expressions of SLC7A11 and GPX4 increased, the content of IL-6 in the PBMC supernatant decreased but the content of TNF-α increased, and the differences were statistically significant. In contrast, the inducer group, when compared to the RA group, displayed increased ROS levels, reduced expression of SLC7A11 protein and mRNA and decreased expression of Nrf2 protein, and the contents of TNF-α and IL-1 in the PBMC supernatant increased, but the expression of GPX4 protein increased, and the differences were statistically significant. The inducer group, compared to the RA group, showed increased cell viability, and the difference was statistically significant(P<0.000 1). Conclusion The presence of ferroptosis in PBMC in RA patients, inhibiting or inducing PBMC ferroptosis in RA patients, will inhibit or promote the secretion of inflammatory factors. Inhibition of PBMC ferroptosis in RA patients may be helpful in the treatment of RA.