The aim of the study is to investigate whether the functional p53 codon 72 polymorphism is associated with susceptibility to SLE and its clinical features. A polymerase chain reaction of genomic DNA-restriction fragment length polymorphism was used to determine genotypes of the p53 codon 72 in 90 SLE patients and 114 healthy controls. Clinical/serological manifestations were analysed in each patient and correlated with the genotypes. The OR of the association of the Pro allele with SLE was 1.70 (95% CI, 1.15-2.53, P = 0.0079) and the OR of the Pro/Pro (a recessive model) was significantly increased (OR = 2.58, 95% CI = 1.24-5.39, P = 0.0093). The Armitage's trend test indicated a significant dosage effect of the Pro allele for SLE (OR = 1.73, chi-square = 7.08, P = 0.0078). However, there was no significant association of the polymorphism with clinical/serological manifestations studied here. In conclusion, our finding suggests the functional p53 codon 72 polymorphism may be associated with SLE susceptibility, suggesting individuals who carry the Pro allele may have a higher risk to SLE susceptibility than those with the Arg allele. Further studies for replications are needed to confirm that the p53 polymorphism contributes to SLE.