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Simple Summary: Hepatocellular carcinoma (HCC) is the most common form of liver cancer with a low survival rate worldwide. The number of new cases and deaths from HCC is increasing globally, thus, we investigated the clinical conditions and survival of patients in Ethiopia to understand the extent of the problem and develop prevention and control strategies. Our analysis showed that hepatitis B virus (HBV) is an important risk factor associated with HCC. Half of the patients involved in our study survived only for about 5 months after their diagnosis. Patients who had been given antiviral therapy for an HBV infection survived longer than those who were not treated. By the year 2040, there will be a two-fold increase in the number of cases and deaths from HCC in Ethiopia. Therefore, since HBV is a major underlying factor for HCC, it is crucial to increase the vaccination coverage and access to antiviral drugs against hepatitis to lessen the devastation. (1) Background: Hepatocellular carcinoma (HCC) is one of the deadliest cancers globally, killing over 700,000 people each year. Despite the rising incidence and mortality rates of HCC in Ethiopia, only few single-centered studies have been conducted; therefore, we aimed to explore the clinicopathological characteristics and survival of patients with HCC in multicenter settings. (2) Methods: We conducted a retrospective analysis of 369 patients with confirmed HCC diagnosed between 2016 and 2021. The survival of patients weas determined using the Kaplan–Meier method, and hazard ratios of the prognostic factors were estimated in Cox proportional hazard models. (3) Results: Majority patients were male (67%) and had a mean age of 52.0 ± 15.6 years. The majority of patients (87%) had a large tumor size (>5 cm) at diagnosis and presented with an advanced-stage condition. Cirrhosis (58%) and viral hepatitis (46.5%) were the main risk factors associated with HCC. The median overall survival was 141 days (95% CI: 117–165). Patients who took antivirals for HBV had a higher survival benefit compared to the untreated group (469 vs. 104 days; p < 0.001). The risk of death was 12 times higher in patients with Barcelona Clinic Liver Cancer-D (BCLC-D) terminal stage HCC compared to patients with an early stage (BCLC-A) HCC. The stage of HCC and treatment against HBV are the most significant survival predictors. (4) Conclusions: The overall survival of HCC patients in Ethiopia is poor. Cirrhosis and viral hepatitis are the primary risk factors linked with HCC. Patients who received antiviral therapy for HBV had a better survival outcome. [ABSTRACT FROM AUTHOR]