rs2431697 is located on 5q33.3, between pituitary tumor-transforming gene 1 and miR-146a. Several studies have estimated the association between rs2431697 and systemic lupus erythematosus risk. However, the results were inconsistent. A case-control study was carried out to explore the association between rs2431697 and systemic lupus erythematosus risk in a central Chinese population. Meta-analyses combining present with previous studies were conducted to further explore the association. Our case-control study included 322 cases and 353 controls. rs2431697 T allele was associated with increased risk of systemic lupus erythematosus (odds ratios (ORs) = 1.461, 95% confidence intervals (CI) 1.091-1.957, P = 0.011). The association was stronger between T allele and the risk of anti-double-stranded DNA (dsDNA)-positive systemic lupus erythematosus (OR = 2.510, 95% CI 1.545-4.077, P < 0.001). The meta-analyses included 8648 systemic lupus erythematosus patients and 10947 controls. rs2431697 T allele had an overall OR of 1.262 (95% CI 1.205-1.323, P < 0.001) under fixed-effects model. After stratified by ethnicity, I (2) reduced from 24.3 to 0 %. T allele had an OR of 1.213 (95% CI 1.145-1.284, P < 0.001) in European descendant and 1.365 (95% CI 1.259-1.480, P < 0.001) in Asian under fixed-effects model. Data on women were also extracted, and T allele had an OR of 1.337 (95% CI 1.162-1.539, P < 0.001) under random-effects model. The pooled ORs were not influenced by each study in sensitivity analyses. There were no publication biases observed in these analyses. The results from our case-control study and the meta-analyses indicate that rs2431697 T allele significantly associates with the increased risk of systemic lupus erythematosus.