In a population-based survey, Hepatitis B virus (HBV) infection status, associated risk factors and vaccine coverage among the 4006 Particularly Vulnerable Tribal Groups (PVTG) participants of Odisha Tribal Family Health Survey (OTFHS) were assessed using various viral markers. All the HBsAg-positive sera were screened for viral load estimation, envelopment antigen (HBeAg) identification and liver profile parameters. The overall prevalence of HBsAg was 5.73% and the Kutia Khond tribes showed highest prevalence (17.85%; 95% CI:17.41–18.29) of HBsAg. Only 2.7% of children born following the implementation of hepatitis B vaccination were HBsAg positive. Among the children between 0 and 36 months, the vaccination coverage was 91% and mean Anti-HBs titre was 142.56 mIU/ml. Tattooing and piercing were found to be positively associated with high HBsAg positivity. Abnormal liver function (high SGOT and SGPT) occurred more often in HBeAg positive with high viral loads (> 2000 IU/ml). Given the high prevalence of HBV DNA with active viral replication, a strategy for regular monitoring and treatment of these individuals combined with risk factor management and health education in this indigenous population is urgently needed.