Protein C deficiency is one of the causes of curable or preventable portal vein thrombosis. We report two patients of portal vein thrombosis associated with hereditary protein C deficiency. The first patient presented with continuous right upper quadrant pain and high fever. The abdominal sonography revealed normal liver parenchyma but portal vein and superior mesenteric vein thrombosis. Based on a 55% (normal 70-140%) plasma protein C level, he was diagnosed as having protein C deficiency. A trace of his family history showed that his elder brother also had protein C deficiency with a 50% plasma C level. Both patients received anticoagulant therapy. The younger brother showed good response. Unfortunately, the elder one suffered from recurrent episodes of variceal bleeding and received a life-saving splenectomy and devascularization. We herein remind clinicians that early screening and therapy are helpful in preventing late complications of protein C deficiency with portal vein thrombosis.