IL-1R antagonist–deficient (Il1rn−/−) mice develop autoimmune arthritis in which IL-17A plays a crucial role. Although many studies have shown that Th17 cell differentiation is dependent on TGF-β and IL-6, we found that Th17 cells developed normally in Il1rn−/− Il6−/− mice in vivo. Then, we analyzed the mechanisms of Th17 cell differentiation in Il1rn−/− Il6−/− mice. We found that IL-21 production was increased in the lymph nodes of Il1rn−/− mice, naive Il6−/− CD4+ T cells differentiated into Th17 cells when cultured with TGF-β and IL-21, and the differentiation was greatly enhanced when IL-1 was added to the culture. Th17 cell differentiation was not induced by either TGF-β or IL-1 alone or in combination. IL-21 induced IL-1R expression in naive CD4+ T cells, and IL-1 inhibited TGF-β–induced Foxp3 expression, resulting in the promotion of Th17 cell differentiation. Furthermore, IL-1 augmented the expression of Th17 cell–specific transcription factors such as Nfkbiz and Batf. These results indicate that excess IL-1 signaling can overcome the requirement of IL-6 in the differentiation of Th17 cells by suppressing Foxp3 expression and inducing Th17 cell–specific transcription factors.