OBJECTIVES: Sorafenib, an oral targeted-therapy, is commonly used to treat unresectable hepatocellular carcinoma (HCC). Although the concern of QTc prolongation is pin-pointed in the package insert, it is unknown clearly about its incidence, especially in HCC patients. This study aimed to explore the incidence and factors associated with sorafenib-induced QTc prolongation in HCC in Taiwan. METHODS: In this retrospective study, we reviewed medical records in a medical center in Taiwan for those patients treated with sorafenib at the first time during January 1^st to December 31th, 2019. Those patients with ECG at baseline and more tests of ECG during four-months treatment but not more than seven days after the end of treatment were included. Those patients with phenomena of QTc prolongation (≥ 450 ms) at baseline, and/or had a pacemaker-driven rhythm were excluded. The maximum QTc result during the follow-up period was identified to categorize its severity of event based on Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The patients’ demographic and clinical characteristics were compared between the groups with or without the event using χ² test to explore the associated factors. RESULTS: Of 296 patients using sorafenib, 52 were incident users. Their average age at treatment was 65 ± 11 years, and 58% of them were male. While average QTc at baseline was 424 ± 19 ms, the incidence of QTc prolongation was 30.8% and 7.7% of occurrence were categorized as grade 3. The average time to reach the highest ECG was 56 ± 31 days. Those patients with hypertension tended to encounter the events than those without hypertension (p = 0.049). CONCLUSIONS: While incidence rate of sorafenib-induced QTc prolongation in HCC patients was relative high, having sufficient time to closely monitor ECG, especially for whom were hypertension, are necessary to avoid severe cardiotoxicity.