Purpose: The purpose of this study was to compare quality of life (QoL) after two different transarterial therapies [transarterial chemoembolization (TACE) and transarterial radioembolization (TARE)] for patients with unresectable hepatocellular carcinoma (HCC) to assess tumor therapy in palliative situation additional to traditional aims like survival or image response. Material and methods: QoL was evaluated with two validated questionnaires (EORTC QLQ-30 and EORTC HCC18) before and 14d after treatment in 94 initial therapies (TACE n = 67; TARE n = 27). QoL changes after treatment were analyzed. Tumor response was evaluated using RECIST/WHO/mRECIST/EASL criteria. A multivariate linear regression was undertaken to identify potential influence factors on change of QoL. Results: Mean return rate of questionnaires was 71.3% allowing analysis of 67 therapies (TACE n = 46; TARE n = 21). Initial global health status/QoL was significantly higher in TACE (62.5%) compared to TARE with 50.8%. Absolute global health decrease was higher in TACE (− 10.5%) compared to TARE (− 4.8%, p = 0.396). Also relative global health decrease was higher in TACE (− 16.82%) compared to TARE (− 9.37%). Findings for other items were corresponding, as less impairment was found for TARE compared to TACE for physical/social functioning, fatigue and pain. Objective mRECIST response rate was 22.8% in TACE and 21.1% in TARE. Conclusion: Neither TACE nor TARE showed a major decrease in QoL after first treatment. TACE showed a slightly but not significantly higher decrease, so this study is not clearly in favor for one treatment. But with the addition that TARE showed less decrease even in patients with higher tumor burden and lower baseline.