Gold nanocages (AuNCs) were synthesized via galvanic replacement method and characterized by TEM and UV-Vis-NIR. In order to investigate the adjuvant potential of AuNCs, AuNC-formulated recombinant Hepatitis B surface antigen (HBsAg) preparations were used. First, the adsorption efficiency and cumulative release percentage of newly created HBsAg-AuNC formulations were characterized. Then, their adjuvant responses in RAW 264.7 macrophages were systematically analysed in vitro by real time cell analysis system, flow cytometry, confocal microscopy, and ELISA. We have observed that HBsAg-AuNC vaccine formulations were stable and have uptaken easily by macrophages but not into the nucleus, and triggered the immune maturation of RAW 264.7 cells. Here in vitro studies have shown that Au nanocages with superior properties may be considered as a new adjuvant candidate alternative to alum.