Gelatin sponge particles are commonly used in the conventional transarterial chemoembolization (c-TACE) as an adjuvant embolizing agent for hepatocellular carcinoma (HCC). However, there are few reports regarding the clinical applications of gelatin sponge microparticles (GSMs) as a main embolizing agent in the treatment of HCC. This retrospective study aim to evaluate the efficacy and safety of patients with Barcelona Clinic Liver Cancer (BCLC) stage B HCC treated with intra-arterial injection of 350 to 560 μm GSMs mixed with anticancer agents.Twenty-four patients with unresectable BCLC stage B HCC without any prior treatment underwent transarterial chemoembolization with gelatin sponge microparticles (GSMs-TACE) of diameter 350 to 560 μm mixed with lobaplatin. The mixture was injected into tumor-feeding arteries until the sluggish flow in selective artery. Safety was measured by assessing complication rate, and efficacy was reflected by assessing response to mRECIST therapy and overall survival. The survival rate was calculated using the Kaplan–Meier method.All 24 BCLC stage B HCC patients showed good tolerance to the procedure. The mean follow-up period was 27 months and mean number of TACE treatments per patient was 3.7 sessions (range 1–10) during the follow-up period. Postprocedure complications were mild and treated by symptomatic treatment. Six months and 1 year overall survival rates were 100% and 87.5%, respectively. Overall median survival time was 25 months (95%CI: 21.06–28.95 months).GSMs-TACE is a safe and effective method for BCLC stage B HCC patients.