Smad ubiquitylation regulatory factor 1 (Smurf1) has been identified to play a critical role in bone homeostasis, development, cell cycle regulation and tumorigenesis. However, the role of Smurf1 in macrophage proliferation, apoptosis and migration is still unclear. Here, we show that Smurf1 expression was elevated in LPS-induced RAW264.7 macrophage and mouse embryonic fibroblasts (MEFs). And we found that knockdown of Smurf1 suppresses macrophage proliferation but promotes apoptosis and migration. Furthermore, JNK and p38 MAPK signaling were upregulated in Smurf1-depleted cells. And inhibition of JNK and p38 MAPK signaling in Smurf1 knockdown cells rescue the phenotypes of macrophage proliferation, apoptosis and migration. Therefore, our study suggests that Smurf1 is a new positive regulator for macrophage proliferation and apoptosis, but a negative regulator for macrophage migration.