Background <p>Despite several reports of poor treatment outcomes for hepatocellular carcinoma, there is a paucity of data about the treatment outcome of this cancer in our setting. Hence, this study aimed to investigate the treatment outcomes of hepatocellular carcinoma patients at Kenyatta National Hospital.</p> Methods <p>A hospital-based retrospective cohort study was conducted on 73 eligible hepatocellular carcinoma patients treated at the facility from 1st January 2017 to 31st December 2022. To obtain relevant data from the files of the patients, the study used a data abstraction tool. The collected data were analyzed using the Statistical Package for Social Sciences, version 20.0 statistical software. The Kaplan-Meier survival analysis and Cox proportional hazard regression were used to assess the median survival time and predictors of mortality, respectively.</p> Results <p>More than half of the patients were deceased (61.6%) after treatment. Furthermore, most patients had evidence of distant metastasis (58.9%), disease relapse (53.4%), and disease progression (46.6%) during the follow-up period. The median cancer-specific survival time was 20.8 ± 2.6&#xa0;months. On the other hand, the cancer-specific survival after metastasis and metastasis-free survival were 14.0 ± 2.4&#xa0;months and 19.6 ± 4.7&#xa0;months, respectively. Patients with distant metastasis (AOR = 2.5, 95% CI = 1.5–4.2, <i>p</i> &lt; 0.001) and received chemotherapy (AOR = 3.6, 95% CI = 1.4–9.0, <i>p</i> = 0.007) had a higher hazard of mortality.</p> Conclusion <p>Most of the patients had distant metastasis, disease progression, and deceased during their last follow-up period, showing a poor treatment outcome. Distant metastasis and chemotherapy were the significant predictors of mortality. Hence, treatment strategies should be shifted from conventional chemotherapy to more effective targeted therapies to reduce mortality and disease progression.</p>