The WHO aims to detect 90% of global cases of hepatitis B virus (HBV) by 2030. Sub-Saharan Africa carries a disproportionate burden of HBV and hepatocellular carcinoma (HCC). In this study, we sought to assess the utility of a combined HBV and HCC screening program in Tanzania. We conducted a prospective, serial cross-sectional study of patients who participated in a combined HBV and HCC screening program at a regional referral hospital emergency department (ED) in Arusha, Tanzania, between April 19, 2022 and June 3, 2022. All patients completed a study questionnaire and were tested for HBV surface antigen. Patients who were HBV positive were screened for HCC via point-of-care ultrasound (POCUS). The primary outcome was the number of new HBV diagnoses. Data were analyzed with descriptive statistics. A total of 846 patients were tested for HBV (primary ED: 761, clinic referral: 85). The median age of patients was 44 ± 15 years, and 66% were female. Only 15% of patients reported having a primary care doctor. Thirteen percent of patients had been previously vaccinated for HBV. There were 17 new HBV diagnoses (primary ED: 16, clinic referral: 1), which corresponds to a seroprevalence of 2.0% (95% CI: 1.2%, 3.2%). No patients had liver masses detected on POCUS. An ED-based, combined HBV and HCC screening protocol can be feasibly implemented. This study could serve as a model for HBV/HCC screening in regions with high HBV endemicity and low rates of community screening.