Tumor lysis syndrome (TLS) is a potentially lethal complication in cancer therapy. It may occur in highly sensitive tumors, especially in childhood cancer and leukemia, whereas, it is rare in the treatment of solid tumors in adults. TLS results from a sudden and rapid release of nuclear and cytoplasmic degradation products of malignant cells. The release of these can lead to severe alterations in the metabolic profile. Here, we present two cases of large hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE) that resulted in TLS. Although TLS rarely happens in the treatment of adult hepatic tumor, only a few cases have been reported. We should keep in mind that all patients with HCC, particularly those with large and rapidly growing tumors, must be closely watched for evidence of TLS after TACE.