Background: Hepatocellular carcinoma (HCC) is the 3rd leading cause of cancer-related death worldwide. The majority of HCCs are diagnosed in a stage that is not eligible for curative resection. For intermediate stage HCC, transarterial chemoembolization (TACE) is the recommended treatment. We evaluated the safety and efficacy of DSM (degradable starch microspheres) as embolic agent in transarterial chemoembolization (TACE) for the treatment of intermediate stage, non-resectable hepatocellular carcinoma (HCC). Methods and Findings: A national, multi-center observational study on the safety and efficacy of DSM-TACE for the treatment of intermediate HCC was conducted. The recruitment period for the study was from January 2010 to June 2014. The primary endpoints were safety and treatment response according to the mRECIST criteria. A total of 179 DSM-TACE procedures in 50 patients were included in the analysis. The therapeutic efficacy assessed with mRECIST was as follows: complete response (n=1; 2 %), 21 partial response (42 %), 13 stable disease (26 %), 9 progressive disease (18 %), and 6 incomplete data (12 %). Thus, the objective response rate was 44% (n=22) and disease control rate was 70% (n=35). A total of 76 immediate adverse events (AE) and 2 severe adverse events (SAE) were recorded. Forty-eight percent of patients (n=24) did not encounter any immediate AE/SAE. Between treatments, a total of 66 AE and one SAE were recorded. Twenty-four patients (48 %) did not encounter any AE/SAE in between treatments. Conclusion: The use of DSM as a TACE embolic agent appears to be safe for the treatment of HCC and has promising efficacy.