Background p53 is a tumor suppressor and plays a key role in regulating cell hyperplasia, repairing DNA and inducing apoptosis. This study was to investigate p53 expression in fibroblast-like synoviocytes (FLS) and its effect on CD4+ T lymphocytes from patients with active rheumatoid arthritis (RA).Methods Human FLS were transfected with p53 siRNA and cocultured with CD4+ T lymphocytes from patients with active RA. The expressions of osteoprotegerin and interleukin (IL)-6 were detected in p53 siRNA and scramble siRNA-transfected FLS. In addition, protein levels of interferon (IFN)-γ, IL-17, IL-4 and CD25 as well as mRNAs of IFN-γ,retinoic acid-related orphan receptor (ROR)-γt, IL-17 and Foxp3 in cocultured CD4+ T lyrmphocytes were also measured.Results IL-6 decreased in p53-knockdown FLS while osteoprotegerin expression was not altered. FLS with p53 deletion significantly increased the production of IL-17 and IFN-γ by CD4+ T cells and upregulated Foxp3 mRNA expression without effects on the proportion of CD4+CD25high T lyrmphocytes.Conclusion p53 in FLS might regulate Th1 and Th17 functions in patients with RA and participate in the pathogenesis of RA.