Objectives. According to recent reports, prophylactic use of antibiotics is not always required in conventional transarterial chemoembolization (c-TACE). However, clinical evidence of prophylactic antibiotics in drug-eluting beads transarterial chemoembolization (DEB-TACE) to prevent postsurgical infection is limited. This study is aimed to evaluate the correlation between the preoperative prophylactic application of antibiotics and postoperative infection in c-TACE or DEB-TACE, especially in a population with a high risk for postsurgical infection. Methods. In this retrospective study, TACE patients diagnosed with hepatic carcinoma (between January 2019 and May 2021) were examined. The case group was given 1.5 g cefuroxime sodium 0.5–1 hour before TACE, while there was no intervention in the control group. The outcomes analyzed were leukocyte count >9.5 × 109/L on the second day after the operation and the diagnosis of infection within one month after the operation. We applied univariate, multivariate logistic regression, trend analysis, and subgroup analysis to find potential risk factors and the necessity of prophylactic antibiotics. Results. Among 142 eligible cases, 72 received antibiotics while 70 were kept as control, 113 cases were treated with c-TACE, and 29 were treated with DEB-TACE. Multivariate analysis showed that the increase in white blood cell count after the operation was related to diabetes (OR 5.112, 95% CI 1.229–21.264, p = 0.025). The occurrence of postoperative infection was negatively correlated with preoperative albumin value (＜25 g/L) (OR 153.118, 95% CI 1.631–14372.331, p = 0.030). Trend analysis showed that the risk of postoperative infection increased with a decrease in serum albumin level (P < 0.05). Subgroup analysis showed that there were no significant differences in the incidence of increased leukocyte count and postoperative infection between the prophylactic and nonprophylactic treatment groups, in the case of diabetes, preoperative albumin levels, and operation mode (P > 0.1). Conclusions. Prophylactic antibiotic treatment before the c-TACE or DEB-TACE had no significant correlation with postoperative leukocyte increase and postoperative infection. Diabetes history and serum albumin levels were the prominent risk factors associated with an increase in postoperative leukocyte count and postoperative infection. Future large-scale studies and randomized-controlled trials are required to confirm and validate this association.