To compare the survival and initial imaging response of conventional transarterial chemoembolization (TACE) performed with a mixture of lipiodol with Doxorubicin followed by microspheres embolization (cTACE) versus drug-eluting embolic transarterial chemoembolization loaded with Doxorubicin (DEE-TACE) for the treatment of unresectable hepatocellular carcinoma (HCC). Retrospective single-center study, with consecutive patients who underwent TACE for unresectable HCC from January 2005 to December 2016. Patients who received contemporary adjuvant treatment (radiofrequency, microwave or alcoholization) were excluded. Variables analyzed were gender, age, etiology of chronic liver disease, MELD-Na score, Child-Pugh classification, size, location and number of HCC, diameter of the larger HCC and number of TACE sessions. The primary endpoint was survival, measured as time from first TACE to death. Secondary endpoint was imaging response to TACE, assessed using modified response evaluation criteria in solid tumors (mRECIST), which classifies patients in complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD). Statistical analysis was performed using t-test for continuous variables and chi2 for categorical variables, the survival rates were calculated by Kaplan–Meier method and survival curves were compared using log-rank test. A value of p <0.05 was considered statistically significant. 109 patients underwent TACE, 79 received cTACE and 30 DEB-TACE. Significant differences between both groups were observed in the number of TACE sessions (higher in cTACE group, p = 0.035). Survival at 1-, 2- and 3-years were 67%, 34% and 27% for cTACE group and 72%, 64% and 64% for DEE-TACE group, respectively (p = 0.113). After treatment, CR, PR, SD and PD were 29 (53%), 11 (20%), 12 (22%) and 3 (5%) for cTACE group, and 10 (44%), 9 (39%), 4 (17%) and 0 for DEE-TACE group, respectively (p = 0.299). No significant differences in terms of survival or initial imaging response between cTACE and DEE-TACE were observed in the present study. However, there is a tendency for a higher survival rate in DEE-TACE group.