In clinical practice, it is difficult to monitor the repeating relapse in patients who have been suffering from systemic lupus erythematosus (SLE). The underlying etiology remains largely unknown. In order to understand the pathogenesis of SLE, the renal tubular cells-derived iPSCs were successfully obtained from urine of SLE patients. Here, with the purpose of identifying differentially expressed genes, highthroughput Illumina sequencing technology were analyzed the mRNA expression in SLE-iPSCs group and control-iPSCs group. Within the 4,254 genes, which were differentiated at least two-fold between the SLE-iPSCs and control-iPSCs, 2,856 genes were up-regulated and 1,398 down-regulated. These differentially expressed genes were involved in 9 cellular components, 9 molecular functions, 8 biological processes and 6 pathways with p-value ≤ 0.05. The clusters of “cellular process”, “intracellular” and “binding” represented the largest group in Process Ontology, Component Ontology, Function Ontology, respectively. Most differentially expressed genes involved in Function of binding, which were reported to be relevant with RNA transcription in SLE. Moreover, alternative splicing events and gene structure refinements of SLE-iPSCs group were greater than those of control-iPSCs group. Occurrence and development of SLE may be related to the excessive alternative spliced genes and events of alternative splicing. Using large cohorts of patient samples with long-term clinical follow-up data deserves for further investigation and research. Thus, it could assess the usefulness of the pathogenesis of SLE.