White spot syndrome virus (WSSV) is a major viral pathogen in global shrimp farming, causing huge economic damage. Through penetrating the outer surface of the target tissues, WSSV enters into the cells of the target tissue to complete the replication process in the host. In the present study, a cuticle protein gene from Litopenaeus vannamei, designated as LvAMP13.4, was identified and proved to be involved in WSSV invasion. The deduced amino acid sequence of LvAMP13.4 contained a signal peptide and a conserved chitin-binding domain type 4 (ChBD4). This cuticle protein gene was mainly expressed in stomach, gill and epidermis. The expression level of LvAMP13.4 was significantly changed during WSSV infection. Silencing of LvAMP13.4 by dsRNA interference apparently reduced the mortality rate and the WSSV copy number in shrimp upon WSSV infection. Furthermore, yeast two-hybrid system and Co-IP assay were performed to confirm that LvAMP13.4 could interact with the major envelop protein VP24 of WSSV. These data indicated that LvAMP13.4 was involved in the invasion process of WSSV through interaction with VP24. The present results could provide new insights for us in understanding the role of host cuticle proteins during virus invasion.