Tumor lysis syndrome (TLS) occurring after surgical resection of right atrium (RA) and inferior vena cava (IVC) tumor thrombus is a very rare but insidious condition. We report a case of hepatocellular carcinoma who developed TLS after uneventful excision of RA+IVC tumor thrombus under median sternotomy and cardiopulmonary bypass (CPB). Although the procedure was not expected to arouse massive tumor cell necrosis, post-operative course was complicated by metabolic acidosis, hypocalcemia, and progressive hyperkalemia indicative of TLS. Unfortunately, laboratory diagnosis of TLS was delayed under conditions of continuous renal replacement therapy (CRRT) for peri-operative acute renal failure. Despite all efforts, the patient died 36 hours after surgery due to lethal arrhythmia and disseminated infarction of the kidneys, spleen, and liver.