Adjuvant can be used to enhance the immunogenicity of antigen and improve the efficacy of vaccine. Potent adjuvant action is often correlated with NF-kB activation, as exemplified by the case of MPL or LPS. However, NF-kB activation is thought to play an important role in the development and/or maintenance of many types of cancer. The potential of phyto-compounds to modulate NF-kB offers a fruitful field of research into exploiting this clinically relevant transcription factor. We have therefore set to study the possible adjuvant role of polysaccharide and phyto-compounds in the development and progression of murine B16 melanoma by using DNA vaccine model. The human melanoma-associated antigen, hgp100, expression vectors were transfected into mouse skin via gene gun delivery, and followed by subcutaneous application of various phyto-compound formulations onto testing mouse skin tissues. We hypothesize that Dioscorea polysaccharide (Dx-I) might mimic the functions of exogenous danger signals to mammalian immune cells. We observed that co-administration of low dose Dx-I or LPS with the test DNA vaccine could significantly protect from tumor cell challenge with gp100-B16 melanoma cells, as compared to high dose and no treatment groups. On the other strategy, using anti-inflammatory compounds can partially filtrate the inflammation-associated tumorigenesis which elicited by Dx-I or LPS. Our data indicated that use of adjuvant containing LPS combination with emodin (an anti-inflammatory phyto-compound) has lowest tumor size and highest survival percentage than other adjuvant treatment and control in melanoma DNA vaccine model. These results suggest that balance the expression level of NF-kB is important in tumorigenesis and vaccination.