Background: The hepatitis B virus (HBV) is responsible for causing a communicable liver disease that can be prevented through vaccination. Although the HBV vaccine was introduced in Kenya’s expanded immunization program in 2003, the incidence of HBV remains high in the country, especially among IDUs. Objective was to investigate the influence of socio-cultural factors on HBV infection in Mombasa County, Kenya. Methods: The study utilized a cross-sectional analytical design. The study was purposely conducted in Mombasa County because the area is highly prevalent with drug users and people with hepatitis B. There are eight treatment centers in the county, 4 public and 4 privates where stratified random sampling was used. The sample size was proportionately distributed across the selected treatment centers. The study employed a mixed method of data collection, involved; self-administered questionnaire to the IDU’s, key informant interviews and focused group discussion with treatment care managers. Results: The prevalence of hepatitis B was 22%; with male (77.1%) most affected than women (22.9%). Bivariate analysis show that a history of drug abuse was significantly associated with prevalence of hepatitis B (χ2=2.485, df=1, p=0.046). Conclusions: The prevalence of hepatitis B is on the increase among injecting drug users. Having a history of drug abuse was a significant predictor to the prevalence of hepatitis B among injecting drug users in this study. Cultural practices such as piercing and tattooing were observed among study participants were established as a risk factor to hepatitis B infection among injecting drug users.