The non-response to hepatitis B vaccine in health care workers (HCWs) is reported to vary between 5 and 40%. The underlying cellular and molecular events for unresponsiveness to HBV vaccine have not yet been characterized at any great extent. In the current study, we examined the CD150 surface expression levels and its association with polyclonally activated and HBV specific stimulated cellular proliferations in responders and non-responders. CD150 was identified as upregulated expression marker with suppressive regulatory cell function on all activated T cells by gene chip analysis. We found the overall weak cellular proliferation in response to specific and non-specific agents in non-responders. This is significantly associated with enhanced surface expression of CD150 in the non-responders. A strong expression of CD150 with weak cellular proliferation could be used as a predictive marker for non-responsiveness.