Aims: Locoregional therapies, such as yttrium-90 (Y-90) radioembolization (RE) and conventional chemoembolization (CE) can effectively control localized hepatocellular carcinoma (HCC) in patients who are not amenable to curative resection. However, it has not yet been fully established which modality is more effective. The aim of this study was to compare effectiveness of RE and CE as the first treatment of HCC. Methods: We retrospectively reviewed data of patients who received RE or CE as the first treatment of HCC at Seoul National University Hospital from March 2012 to December 2017. A propensity score matching was performed to reduce selection bias. Overall survival (OS), progression-free survival (PFS), and intrahepatic PFS were compared. Results: A total of 138 patients who were initially treated with RE (n=54) or CE (n=84) was included in this study and baseline characteristics was well-balanced between the two groups. Of 138 patients, median age was 59 and median follow-up period was 22.5 months. RE showed better overall survival than CE (hazard ratio [HR]=0.30, 95% confidence interval [CI]=0.10- 0.90, log-rank P=0.02) and tended toward better intrahepatic PFS than CE (HR=0.52, 95% CI=0.25-1.09, log-rank P=0.08). However, progression-free survival was not significantly different between the two groups (HR=0.67, 95% CI=0.39-1.16, log-rank P=0.15). In multivariable analysis, RE was an independent prognositc factor for overall survival (adjusted HR=0.31, 95% CI=0.11-0.92, P=0.04). Conclusions: RE might be more effective as the initial treatment than CE in patients with HCC.