Background: Nasopharyngeal carcinoma (NPC) is a prevalent malignant tumor in Southeast Asia. The management of NPC has remained a challenge until now. ELF-1 is a member of the ETS family of transcription factors that regulate genes involved in cellular growth. ELF-1 expression has been reported in various cancers and is required for tumor growth and angiogenesis; however, its function in NPC remains unclear. In the present study, we characterized the role and underlying mechanism of ELF-1 in NPC. Methods: The biological functions of ELF-1 in NPC cells such as proliferation, migration, invasion, and drug resistance were investigated using MTT, BrdU incorporation, and Transwell assays. To gain more insight into the mechanism of ELF-1 in NPC, we analyzed CCL2/CCR2 signaling by Western blotting, ELISA, siRNAs, and CCR2 antagonist. Results: Gain-of-function of ELF-1 in TW01 and TW04 cells promoted NPC cell proliferation, BrdU incorporation, migration, invasion and cisplatin resistance. By contrast, knockdown of ELF-1 produced opposite results. Overexpression of ELF-1 enhanced the expression of CCL2 via binding to its promoter region and increased the level of the extracellular matrix protein CCL2 in cell culture medium. ELF-1 expression also modulated the downstream targets of CCL2/CCR2 signaling. Most importantly, ELF-1-induced NPC malignant phenotypes were abrogated by a CCR2 inhibitor, implying that the CCL2/CCR2 signaling axis was involved in ELF-1-mediated regulation in NPC. Conclusion: Our data suggest that ELF-1 plays an oncogenic role in NPC development associated with the CCL2/CCR2 signaling pathway and may therefore be a potential target for NPC therapy.