This study aimed to investigate the effects of fusion proteins GnRH-GRP(G3G6)and HSP65-STEAP1(HST1)on dendritic cells(DC)and the sensitization of DCs to B16F10 melanoma. The fusion proteins G3G6 and HST1 were obtained using the previous engineering strains in our laboratory. Group by unsensitized DC(US-DC), the G3G6 fusion protein sensitized DC, the HST1 fusion protein sensitized DC(HST1-DC)and the combined sensitized DC(GH-DC), the mouse bone marrow-derived DCs were sensitized with fusion protein to obtain the fusion protein sensitized DC vaccines. B16F10 melanoma cells were transplanted into C57BL/6J male mice to construct a melanoma model(1×106 cells per mouse), and DC vaccine was injected for treatment. The antitumor efficacy of DC vaccine was explored by in vitro and in vivo experiments. Flow cytometry analysis showed that the fusion protein can effectively stimulate DC into differentiation and maturation; in the animal experiment, the inhibition rate of melanoma treated with G3G6-DC was 35. 75%, that of HST1-DC group and combination group were 34. 03% and 55. 74%. It was initially proved that both G3G6-DC and HST1-DC can effectively inhibit the growth of transplanted tumors of melanoma B16F10 cells in mice, and the combination therapy is superior to the single therapy.