Tumor necrosis factor alpha (TNF‐α)‐induced osteoclastogenesis have profound effects in states of inflammatory osteolysis such as rheumatoid arthritis, periprosthetic implant loosening, and periodontitis. However, the exact mechanisms by which TNF‐α promotes RANKL‐induced osteoclast formation remains poorly understood. B lymphocyte‐induced maturation protein‐1 (Blimp1) is a transcriptional repressor that plays crucial roles in the differentiation and/or function of various kinds of cells including osteoclasts. A novel mechanism was identified where TNF‐α‐mediated Blimp1 expression, which contributed to RANKL‐induced osteoclastogenesis. It is shown that TNF‐α could promote the level of Blimp1 expression during osteoclast differentiation. Silencing of Blimp1 in osteoclast precursor cells obviously attenuated the stimulatory effect of TNF‐α on osteoclastogenesis. Mechanistically, TNF‐α‐induced Blimp1 expression was markedly rescued by blocking the PI3K/Akt signaling pathway, which suggested that PI3K/Akt signaling was involved in the regulation of TNF‐α‐stimulated Blimp1 expression. Taken together, the results established a molecular mechanism of TNF‐α‐induced osteoclasts differentiation, and provided insights into the potential contribution of Blimp1 in the regulation of osteoclastogenesis by TNF‐α. J. Cell. Biochem. 118: 1308–1315, 2017. © 2016 Wiley Periodicals, Inc.