Refractoriness to platelet transfusion indicates a condition in which an expected increase in platelet count is not attained after platelet transfusion. We report herein two cases of refractoriness to platelet transfusion that were caused by the presence of antibodies against the human leukocyte antigen following partial hepatectomy for hepatocellular carcinoma. Due to low postoperative platelet counts in the first case, the patient was transfused with 75 units of platelet concentrate for 3 days after surgery, but was unable to gain a significant increase in the platelet count because of platelet transfusion refractoriness due to anti-human leukocyte antigen antibodies. This case was not complicated and had a favorable clinical course. Despite being transfused with 60 units of platelet concentrate during the 2 days after surgery, the patient's platelet count in the second case did not increase because of the presence of anti-human leukocyte antigen antibodies. Bleeding from the cut surface of the liver into the intraperitoneal cavity was found on the second postoperative day because of a decrease in platelet count. On postoperative day 5, disseminated intravascular coagulation occurred. Perioperative refractoriness to platelet transfusion is an intractable complication since no efficient treatment is available. Preoperative examinations for anti-platelet antibodies should be performed in patients undergoing hepatectomy for hepatocellular carcinoma. This is especially true in cases of decreased platelet counts due to preceding liver cirrhosis and when the prediction for postoperative platelet transfusions is necessary.