Objective: To investigate the protective effects of pcDNA3.1(+)-SjP14 Nano microsphere nucleic acid vaccine on liver injury induced by Schistosoma japonicum in mice. Methods: 30 BALB/c mice were randomly divided into normal saline (NS) group, pcDNA3.1(+)-SjP14 group and Nano microsphere nucleic acid vaccine group, with 10 mice in each group. The mice in each group were respectively injected NS,pcDNA3.1(+)-SjP14 recombinant plasmid and Nano microsphere nucleic acid vaccine through quadriceps femoris (100μg /time,1 time/2 weeks,3 times).2 weeks after the last injection,all the mice were infected by cercaria of S. japonicum,the mice were killed 6 weeks after infection. HE staining was used to observe the pathological changes of liver; as well as the number of eggs, the average diameter, area and volume of single egg granuloma were calculated. Results: General observation and HE staining all showed that the liver pathological changes of mice in NS group were the most serious, while the Nano microsphere nucleic acid vaccine group were the slightest. The number of eggs,the average diameter, area and volume of single egg granuloma of mice in Nano microsphere nucleic acid vaccine group were obviously lower than NS group and pcDNA3.1(+)-SjP14 group (P<0.05). Conclusions: The pcDNA3.1(+)-SjP14 Nano microsphere nucleic acid vaccine has certain protective effects on liver injury induced by S. japonicum in mice.