Dendritic cell (DC) vaccine and fusion protein vaccine have been put into clinical use in cancer immunotherapy. This study compared DC vaccine and fusion protein vaccine directly in their capability of inducing specific immune response. We used mouse Granulocyte Macrophage-Colony Stimulating Factor (mGM-CSF) fused with gastrin-releasing peptide (GRP) and Gonadotrophin Releasing Hormone (GnRH) respectively to obtain mGM-CSF/GRP6 (mG6) and mGM-CSF/mGGn (mGGn) fusion proteins. We prepared fusion protein vaccine and DC vaccine including mG6 protein vaccine (6P), mGGn protein vaccine (nP), mG6 DC vaccine (6D) and mGGn DC vaccine (nD), then the two proteins were mixed to prepare combination proteins vaccine (6nP) and DC vaccine (6nD). After that, C57BL/6 mice were injected with B16F10 cell line to build melanoma tumor model, and were immunized with vaccines to produce antibodies to inhibit and destruct melanoma tumor cells. The discoveries showed that anti- mGM-CSF-GRP6 and anti- mGM-CSF-mGGn antibody vaccines were successfully created as expected; this was deduced from significant inhibition of melanoma tumor in vivo and significant reduction of tumor weight and volume. The effects of DC groups were better than that of the protein groups and the combination of vaccines were more effective than vaccine given separately. Our results indicate that using combination vaccine provides a new strategy to inhibit melanoma tumor growth but a complete cure of melanoma needs further investigations.