Leader RNAs are viral small non-coding RNAs that has been proved to play important roles in viral replication. Snakehead vesiculovirus (SHVV) is an aquatic virus that has caused huge economic loss in Chinese snakehead fish aquaculture industry. It has been proved that SHVV would generate leader RNA during the process of infection, and leader RNA could interact with viral nucleoprotein to promote viral replication. In this study, we identified that leader RNA could also interact with cellular protein Cold Shock Domain containing E1 (CSDE1) and heterogeneous nuclear ribonucleoproteins A3 (hnRNP A3). Further investigation reveals that overexpression of CSDE1 and hnRNP A3 facilitated SHVV replication. Downregulation of CSDE1 and hnRNP A3 by siRNA inhibited SHVV replication. This study provided a new sight into understand the mechanism of SHVV replication, and a potential anti-SHVV target for drug research.