There was established evidence that silencing the attenuator and activating the TLRs could activate the dendritic cells in synergic effects. In this study, we constructed a plasmid, namely pshS1NH, which encodes SOCS1-shRNA, NY-ESO-1-MAGE3 (HLA-A2*0201) fusion antigen and secretory HMGB1, an agent used to modify dendritic cells (DCs), aiming to generate potent DC vaccine against tumors. The SOCS1-shRNA could efficiently downregulate the expression of SOCS1, as indicated by real-time RT-PCR and Western blot. The fusion antigen was detected in the pshS1NH-DCs by PCR and Western blot. Simultaneously, HMGB1 level in the pshS1NH-DCs culture media was significantly higher than that in the control DCs culture media. Levels of Th1 cytokines in pshS1NH-DCs culture media, such as IL-1β, IL-6, TNF-α and IL-12p70, were dramatically higher than those in control DCs culture media. In addition, lymphocytes co-cultured with pshS1NH-DCs secreted dramatically higher level of IFN-γ, whereas no difference was detected in IL-4 levels. Taken together, these data suggest that pshS1NH-DCs may be a potential adjuvant immunotherapy for cancers in clinical applications.