ObjectiveTo clarify the association between miR-146a, miR-499, and IRAK1 polymorphism and systemic lupus erythematosus (SLE) predisposition. MethodsA literature search was conducted until 12 September 2020 in accordance with the PRISMA guidelines. The keywords “miRNA-146a”, “miRNA-499”, “IRAK1” and “SLE” were used in combination to obtain case-control studies evaluating the abovementioned gene polymorphism and the risk of SLE. ResultsPatients harbouring C allele of miRNA-146a rs2431697 exhibited low SLE risk (CC vs. TC+TT, OR=.77, 95% CI=.62–.95, p=.019; TC vs. CC+TT, OR=.84, 95% CI=.71–.98, p=.027; and TC vs. TT, OR=.73, 95% CI=.61–.86, p=.000), whereas patients carrying the A allele and AA genotype of rs3027898 in IRAK1 had significantly decreased SLE susceptibility (A vs. C, OR=.73, 95% CI=.60–.87, p=.001; AA vs. CA+CC, OR=.64, 95% CI=.42–.97, p=.037; AA+CA vs. CC, OR=.71, 95% CI=.56–.88, p=.003, and AA vs. CC, OR=.49, 95% CI=.31–.77, p=.002). No association was observed between miRNA-146a rs2910164 and miRNA-499 rs3746444 with SLE risk. ConclusionThis study demonstrates associations between miRNA-146a and IRAK1 polymorphisms with SLE risk. Larger studies on these associations are needed in the future to support our results.