Radiofrequency ablation (RFA) has become one of the commonly used treatment methods for hepatocellular carcinoma (HCC). It is widely available in the clinic and presents the advantages of short recovery time and a less invasive approach. Only a few complications, such as hemorrhage, ascites, and duct injury, have been reported after RFA for HCC. Herein, we report for the first time the case of a patient diagnosed with recurrent HCC in whom thrombotic thrombocytopenic purpura (TTP) was diagnosed as a complication of the RFA procedure. A 64-year-old male patient with a 2-year history of resected-stage V HCC, in whom later recurrence occurred, underwent RFA for HCC. This patient had a rapid drop in platelets and some petechiae on the wrists after RFA. Combining the clinical and laboratory tests, the diagnosis of TTP was reached. We immediately used plasmapheresis combined with drug therapy, which successfully treated the clinical condition of TTP, with no evidence of recurrence or other complications 1 year after initial treatment. TTP is a rare complication of RFA procedures. Prompt diagnosis and aggressive treatment measures are critical. Through this case report, we hope to raise awareness of the complications of RFA.