ObjectiveTo investigate why the level of Lyn is significantly decreased in B cells from a majority of patients with systemic lupus erythematosus (SLE) and to determine the role of microRNA‐30a (miR‐30a) in SLE B cell hyperactivity.MethodsLuciferase reporter gene assays were performed to identify the interaction between miR‐30a and the 3′‐untranslated region (3′‐UTR) of Lyn. Levels of miR‐30a in B cells were determined by TaqMan quantitative polymerase chain reaction (qPCR), Lyn messenger RNA levels were tested with real‐time qPCR, and protein levels of Lyn were determined using Western blotting. The quantity of IgG was determined by enzyme‐linked immunosorbent assay. The proliferation of B cells was measured using 3H‐thymidine incorporation.ResultsIn B cell lines, miR‐30a, but not miR‐30b, miR‐30c, miR‐30d, or miR‐30e, could specifically bind the 3′‐UTR of Lyn, and overexpression of miR‐30a inhibited the levels of Lyn. The level of miR‐30a in B cells was significantly higher in SLE patients compared to healthy donors. The level of miR‐30a was negatively associated with the level of Lyn in B cells. Overexpression of miR‐30a was found to promote B cell proliferation and the production of IgG antibodies. The effect of miR‐30a could be abrogated by inducing overexpression of Lyn in B cells.ConclusionThese results reveal that elevated expression of miR‐30a is responsible for the reduction in levels of Lyn in B cells from patients with SLE, suggesting that miR‐30a plays an important role in B cell hyperactivity.