Folate-chitosan nanoparticles (FA-CS) were loaded with mouse interferon-inducible protein-10 (IP-10) plasmid DNA to generate FA-CS-IP-10,which was used for immunotherapy in hepatocellular carcinoma (HCC).H22 tumor-bearing mice were treated with FA-CS-IP-10 and tumor targeting was observed by in vivo imaging.Flow cytometry was used to detect the number of myeloid-derived suppressor cells (MDSCs) in tumor and CD4+CD25+FoxP3+ T-regulatory cells (CD4+CD25+FoxP3+ Tregs) in spleen.The enzyme-linked immunospot assay was used to quantify the FA-CS-IP-10-induced tumor-specific cytotoxic T lymphocytes (CTLs) and secretory IFN-γ.IP-10 expression,tumor vessel density,cell proliferation and apoptosis were evaluated by immunohistochemistry.FA-CS-IP-10 significantly inhibited tumor growth,suppressed angiogenesis,increased apoptosis of cancer cells,and prolonged the survival time of H22 tumor-bearing mice.Tumor tissue from FA-CS-IP-10-treated mice had significantly higher IP-10 expression,a lower proportion of Tregs in spleen and higher proportion of MDSCs in tumor and up-regulation of IFN-γ secretion in CTLs compared to the other experimental groups.FA-CS-IP-10 is a promising immunotherapeutic agent for HCC.