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Objective The aim of this study was to analyze the safety and efficacy of glucocorticoid treatment for hyperbilirubinemia in patients with hepatocellular carcinoma (HCC) who have undergone transcatheter arterial chemoembolization (TACE).Methods We conducted a retrospective analysis of the clinical data of 198 patients with HCC who were admitted to The Fifth Medical Center of PLA General Hospital from June 2014 to August 2019 and underwent TACE therapy. The patients were divided into glucocorticoid (GCC) treatment group and control group. Standard liver-protecting procedures were used in both groups. The treatment group also received intravenous injections of methylprednisolone sodium succinate for 3–5 days. Reduction in bilirubin concentration, mean duration of hospitalization, and complications were compared between the two groups to investigate the safety and efficacy of GCCs for treatment of hyperbilirubinemia after TACE treatment. Results Bilirubin concentrations were significantly lower in the treatment group than in control group on days 3 and 5 after GCC/conventional liver-protecting treatment (P < 0.05). The treatment group had significantly shorter durations of total post-surgery hospitalization, and recovery time than the control group (14.5 ± 4.6 days vs. 17.5 ± 6.6 days, P < 0.001; 9.2 ± 3.3 days vs. 11.8 ± 5.4 days, P = 0.001; 7.0 ± 3.3 days vs. 9.3 ± 4.6 days, P < 0.001). No GCC-associated complications were detected in the treatment group. Conclusion Short-term use of GCCs to treat hyperbilirubinemia in patients with HCC who have undergone TACE is safe and associated with rapid decline in bilirubin concentration and shorter hospital stay compared with patients who did not receive GCCs.