Background/Aims: To compare the effectiveness of drug-eluting beaded trans-arterial chemoembolization (DEB-TACE) and conventional trans-arterial chemoembolization (C-TACE) in hepatocellular carcinoma patients treated at Assiut University. Methods: A bi-institutional prospective controlled clinical trial was conducted at both south Egypt Cancer Institute and Assiut University Hospital interventional radiology units in the period from Aug.2019 to Sep.2021. It included 75 patients, fifty of them performed C-TACE, and the other 25 performed DEB-TACE. The evaluation of the target tumor response was done via mRECIST criteria. Conversion to another therapeutic approach, side effects, post-embolization problems, and altered liver function tests were reported.  Results: No significant differences between the two therapeutic modalities although the target tumor response showed a slightly significant tendency in favor of DEB-TACE with a significantly lesser complication as it records a lower frequency of post-TACE syndrome (4 (16%) vs. 18 (36%); p= 0.03), and fever (3 (12%) vs. 20 (40%); p= 0.01). The shift to other treatment modalities was not significantly different between the two groups (P <0.001). Conclusions: DEB-TACE has a better target tumor response with fewer post-embolization complications when compared to C-TACE in advanced HCC and high-risk patients.