Echinococcosis is a worldwide anthropozoonosis which is highly endemic over large animal husbandry areas in northwestern China. The current clinical therapeutic medicine against echinococcosis is albendazole, although it caused serious side effects in patients. The component in traditional Chinese herb medicine, Sophora moorcroftiana alkaloids (SA), is thought to be a potential drug to treat echinococcosis. In order to explore the effect and mechanism of SA treatment against echinococcosis, we established animal echinococcosis model and treated rats with albendazole alone, alkaloids alone, and combined therapy. The combined treatment showed effective inhibition against parasite infection due to induction of host response and alleviated liver injury; meanwhile albendazole caused serious liver problem. The proteomics study revealed that the combined therapy might induce complement activation through C3, C4, C5, SERPINA1, and SERPINC1 proteins and cell adhesion by ANXA2, EZR, YWHAB, HSP90AN1, and PRKAR2A proteins, while albendazole treatment could induce liver injury through CRYAB, YWHAZ, SLC25A24, and HSPA1B proteins that were involved in cell death. In all, we consider that the combinational treatment displayed better therapeutic effects against liver echinococcosis as well as alleviated liver injury, which could be considered as an effective strategy to treat echinococcosis clinically.