Persistent high fever is one typical clinical symptom of hemorrhagic fever with renal syndrome (HFRS) and circulating interleukin-1β (IL-1β) is elevated throughout HFRS. The mechanisms responsible for viral induction of IL-1β secretion are unknown. In the present study, Hantaan virus (HTNV) induced the secretion of IL-1β in the human monocytic cell line THP-1. Induction of IL-1β by HTNV relies on the activation of caspase-1. Small hairpin RNA knockdown in HTNV-infected THP-1 cells indicated that nucleotide-binding domain, leucine-rich repeat containing protein 3 (NLRP3) recruits the adaptor apoptosis-associated speck-like protein and caspase-1 to form an NLRP3 inflammasome complex, crucial for the induction of IL-1β. In HTNV-infected THP-1 cells, reactive oxygen species release, but not extracellular adenosine triphosphate, was crucial for IL-1β production. In conclusion, Hantavirus induces the formation of the NLRP3 inflammasome in THP-1 cells and this may be responsible for the elevated IL-1β levels in HFRS patients.