Background: Hepatocellular carcinoma (HC) is the most common primary tumor of the liver and is a significant health problem worldwide with check-point inhibitors and oral multikinase inhibitors (TKI) as the first-line therapy for advanced diseases. While chemotherapy treatment may not be standardized in current clinical management guidelines, it remains the only available treatment option in numerous Latin American countries. Methods: A retrospective review was carried out, in patients older than 18 years, between January 2011 and December 2020. 127 patients were analyzed and identified, they had received at least one course of chemotherapy at the Instituto Nacional de Enfermedades Neoplásicas in Lima, Perú. Results: The median age was 40 years, 40 female patients (31.5%) and 87 male patients (68.5%). Among the participants, 77 patients (60.62%) were diagnosed with hepatitis B, 2 patients (1.57%) had hepatitis C virus infections, and 48 patients didn´t have viral hepatitis. 72 patients (91.13%) underwent antiretroviral treatment. Non-cirrhotic patients were 118 (92.91%) and 111 (87.4%) had a Child A score. Chemotherapy was administered as first-line treatment to 118 patients (92.91%), with 47.61% receiving 5-FU-based chemotherapy, 11.11% Adriamycin, and 8.7% Gemcitabine-based chemotherapy. A smaller subset, consisting of 8 individuals (6.29%), received sorafenib as their first-line treatment. The overall survival (OS) rates at 12, 36, and 60 months were 74.14%, 20.69%, and 1.72%, respectively. Regarding disease-free survival (DFS) rates at 12, 24, and 48 months were 28.89%, 6.67%, and 2.22%, respectively. Conclusions: In this updated data for advanced hepatocellular carcinoma, we observed a subset of patients with advanced HC achieved favorable outcomes, with a median OS of 20.37 months and a median DFS of 6.6 months. Additional research is necessary to enhance our understanding of the molecular characteristics and resistance pathways of hepatocellular carcinoma in Peru and their correlation with the favorable survival rates observed in response to chemotherapy treatment.