Introduction: Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease affecting predominantly females. To discover additional genetic risk variants for SLE on the X chromosome, we performed a follow-up study of our previously published genome-wide association study (GWAS) data set in this study. Methods: Twelve single nucleotide polymorphisms (SNPs) within novel or unpublished loci with P-value < 1.00 x 10(-02) were selected for genotype with a total of 2,442 cases and 2,798 controls(including 1,156 cases and 2,330 controls from central China, 1,012 cases and 335 controls from southern China and 274 cases and 133 controls from northern China) using Sequenom Massarry system. Associaton analyses were performed using logistic regression with sample region as a covariate through PLINK 1.07 software. Results: Combined analysis in discovery and central validation dataset discovered a novel locus rs5914778 within LINC01420 associated with SLE at genome-wide significance (P = 1.00 x 10(-08); odds ratio (OR) = 1.32). We also confirmed rs5914778 in the southern Chinese sample cohort (P = 5.31 x 10(-05); OR = 1.51), and meta-analysis of the samples from the discovery, central and southern validations regions provided robust evidence for the association of rs5914778 (P = 5.26 x 10(-12); OR = 1.35). However, this SNP did not show association with SLE in the northern sample (P = 0.33). Further analysis represent the association of northern was significantly heterogeneous compared to central and southern respectively. Conclusions: Our study increases the number of established susceptibility loci for SLE in Han Chinese population and has further demonstrated the important role of X-linked genetic risk variants in the pathogenesis of SLE in Chinese Han population.