The anaphylatoxin C3a specific receptor C3aR plays a critical role in the renal diseases, but little is known about the regulation of C3aR expression. Tubulointerstitial hypoxia is common in kidney diseases and is an important pathogenic factor contributing to renal injuries. To investigate whether hypoxia is involved in the regulation of C3aR expression in tubular epithelial cell, in the present study, we investigated the effect of hypoxia on C3aR expression and the underlying mechanism. The human proximal tubular epithelial cells (HK-2) were cultured in hypoxic condition mimicked by addition of NaN₃. The mRNA expression of C3aR was analyzed by quantitative real-time PCR; the protein level of C3aR was evaluated by Western blotting and immunofluorescence. The levels of HIF-1α and NF-κB in nucleus, as well as the effect of HIF-1α or NF-κB inhibition on the expression of C3aR were also examined. We found that hypoxia induced upregulation of C3aR expression both in mRNA and protein level. The protein levels of HIF-1α and NF-κB in nucleus were increased in hypoxic condition. Pre-incubation with HIF-1α or NF-κB inhibitor, both inhibited the C3aR mRNA and protein expression induced by hypoxia. In addition, supplementation with HIF-1α inhibitor decreased the nuclear translocation of NF-κB. These results indicated that hypoxia could induce the expression of C3aR in tubular epithelial cells through HIF-1α/NF-κB pathway.