Objectives. The variant rs3828903 within MICB, a nonclassical MHC class I chain-related gene, was detected to contribute to systemic lupus erythematosus (SLE) in a Caucasian population. This study aimed to investigate the association in a northern Han Chinese population. Methods. We recruited 1077 SLE patients and 793 controls for analysis. rs3828903 was genotyped by TaqMan allele discrimination assay. Using the public databases, its functional annotations and gene differential expression analysis of MICB were evaluated. Results. Significant association between the allele G of rs3828903 and risk susceptibility to SLE was observed after adjusting for sex and age (P = 1.87 × 10(-2)). In silico analyses predicted a higher affinity to transcription factors for allele G (risk) and cis-expression quantitative trait loci (cis-eQTL) effects of rs3828903 in multiple tissues (P ranging from 2.79 × 10(-6) to 6.27 × 10(-38)). Furthermore, higher mRNA expressions of MICB were observed in B cells, monocytes, and renal biopsies from SLE patients compared to controls. Conclusion. An association between rs3828903 and susceptibility to SLE has been detected in a Chinese population. This together with the functional annotations of rs3828903 converts MICB into a main candidate in the pathogenesis of SLE.