To study cell surface receptors of severe fever with thrombocytopenia syndrome virus (SFTSV), the levels of dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) mRNA and SFTSV infection in different cell lines were identified by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). SFTSV-sensitive cells were inhibited by anti-DC-SIGN monoclonal antibody (mAb) and virus infection levels were detected by real-time RT-PCR. Different cell lines were transfected with DC-SIGN-expressing plasmid and SFTSV infection levels either before or after transfection were detected. The results showed that Vero cells which were sensitive to SFTSV had a relatively higher DC-SIGN level than CHO-K1 cells which were less sensitive to SFTSV. Anti-DC-SIGN mAb was capable to inhibit SFTSV invasion into host cells to a certain extent, showing a dose-response effect. The levels of SFTSV infection in cells transfected with DC-SIGN-expressing plasmid were higher than those in non-transfected cells. It is suggested that DC-SIGN is probable one of the cell surface receptors of SFTSV.