Follicular helper T (T<sub>FH</sub>) cells mediate germinal center reactions to generate high affinity antibodies against specific pathogens, and their excessive production is associated with the pathogenesis of systemic autoimmune diseases such as systemic lupus erythematosus (SLE). ETV5, a member of the ETS transcription factor family, promotes T<sub>FH</sub> cell differentiation in mice. In this study, we examined the role of ETV5 in the pathogenesis of lupus in mice and humans. T cell-specific deletion of <i>Etv5</i> alleles ameliorated T<sub>FH</sub> cell differentiation and autoimmune phenotypes in lupus mouse models. Further, we identified <i>SPP1</i> as an ETV5 target that promotes T<sub>FH</sub> cell differentiation in both mice and humans. Notably, extracellular osteopontin (OPN) encoded by <i>SPP1</i> enhances T<sub>FH</sub> cell differentiation by activating the CD44-AKT signaling pathway. Furthermore, <i>ETV5</i> and <i>SPP1</i> levels were increased in CD4<sup>+</sup> T cells from patients with SLE and were positively correlated with disease activity. Taken together, our findings demonstrate that ETV5 is a lupus-promoting transcription factor, and secreted OPN promotes T<sub>FH</sub> cell differentiation.