The anaphylatoxin C5a is a chemoattractant that can induce various inflammatory responses in vivo via the C5a receptor (C5aR). There is emerging evidence that C5a is generated in the cancer microenvironment. However, the role of C5a in human nasopharyngeal carcinoma (NPC) remains largely unclear. Thus, the present study aimed to examine the direct influence of C5a stimulation on the proliferation of human NPC cells and to identify the underlying molecular mechanisms. The effects of C5a stimulation on the proliferation of human NPC cells were studied in vitro, and P300/CBP-associated factor (PCAF)‑mediated signal transducer and activator of transcription 3 (STAT3) acetylation and its role in regulating the proliferation of NPC cells was subsequently explored. Our results demonstrated that C5a stimulation increased the proliferation of human NPC cells in vitro. STAT3 acetylation was further found to be enhanced in human NPC cells induced by C5a. Moreover, PCAF induction was required for STAT3 acetylation in human NPC cells by exposure to C5a. Functionally, PCAF-mediated STAT3 acetylation contributed to the proliferation of human NPC cells stimulated by C5a. These results illustrate the novel activity of the C5a-C5aR axis that promotes human NPC cell proliferation through PCAF‑mediated STAT3 acetylation. This may provide a potential strategy for treating human NPC through inhibition of C5a or its receptors.