The incidence of advanced unresectable hepatocellular carcinoma (HCC) is increasing in developed countries and the prognosis of advanced HCC remains poor. Real-world evidence of treatment patterns and outcomes can highlight the unmet clinical need. We conducted a retrospective population-based cohort study of patients with advanced unresectable HCC diagnosed in Alberta, Canada (2008-2018) using electronic medical records and administrative claims data. A chart review was conducted on patients treated with systemic therapy to capture additional information related to treatment. A total of 1,297 advanced HCC patients were included of whom 555 (42.8%) were recurrent cases and the remainder were unresectable at diagnosis. Median age at diagnosis was 64 (range 21-94) years and 82.1% were men. Only 274 patients (21.1%) received first-line systemic therapy and, of those, 32 patients (11.7%) initiated second-line therapy. Nearly all of the patients received sorafenib (>96.4%) in first-line, and these patients had considerably higher median survival (12.23 months; 95% CI 10.72-14.10) compared with patients not treated with systemic therapy (2.66 months; 95% CI 2.33-3.12; log-rank <0.001). Among patients treated with systemic therapy, overall survival was higher for recurrent cases, patients with Child-Pugh A functional status, and patients with HCV or multiple known HCC risk factors ( <0.05). In a Canadian real-world setting, patients who received systemic therapy had greater survival than those who did not, but outcomes were universally poor. These results underscore the need for effective front-line therapeutic options.