To overcome the low-efficiency toxic side effects and high recurrence of traditional therapy for malignant melanoma, an in situ gel system, HSV-LLCP, was developed as a local treatment for malignant melanoma in this study. This system was based on a lyotropic liquid crystal precursor (LLCP) loading with oncolytic virus herpes simplex virus-1 (HSV-1). With the unique lattice structure, HSV-LLCP, which could enhance the stability of HSV-1 and arrest HSV-1 at the injection site. The performance of LLCP as a virus vector was evaluated comprehensively. The HSV-LLCP showed a rapid gelling property (within 2 s) and the shear viscosity ranged from 5 to 9 mPa·s. The result also revealed the outstanding stability of HSV-LLCP. The release behavior showed a triphasic sustained-release pattern during the experiment period. In addition, HSV-LLCP exhibited a superior oncolytic activity compared to the HSV-1 solution in murine melanoma B16 cells. This study showed that HSV-LLCP would become an alternative and promising HSV-1 vector with high safety and stability for melanoma treatment in the clinic.