Abstract To determine whether the tumor necrosis factor (TNF)-receptor associated factor 1/complement component 5 (TRAF1/C5) polymorphism (rs10818488) confers susceptibility to rheumatoid arthritis (RA) and systemic lupus erythematous (SLE), a meta-analysis was performed. A total of 11 studies with 17 comparisons (11 for RA, 6 for SLE) were available for this meta-analysis, which consisted of 13,456 patients, 12,259 controls for RA and 1,894 patients, 6,729 controls for SLE. A significant association of the A allele of TRAF1/C5 polymorphism (rs10818488) with RA susceptibility was detected in the North Africa population (OR=1.557, 95% CI: 1.225–1.977). Furthermore, the association between this allelic variant and SLE risk was additionally found in population of European (OR=1.247, 95% CI: 1.060–1.466). Analysis also showed the A/G allelic frequency of TRAF1/C5 variant (rs10818488), in different healthy populations, had a different distribution (χ2=269.41, P<0.001). Taken together, our study demonstrates that the TRAF1/C5 polymorphism (rs10818488) may confer susceptibility to RA in North Africa population, and in European population, it might be a contributory factor towards SLE.