Hereditary protein C (PC) deficiency and congenital plasminogen (PLG) deficiency are both factors of thrombophilia which were caused by PC and PLG gene mutations with the characteristics of activity and antigen decreasing inconsonantly. To illustrate the connection between gene mutations and the corresponding deficiencies of PC and PLG, we studied two related cases. The proband 1 showed a cranial venous sinus thrombosis with reduced activities of PC and PLG, 55 and 56%, respectively. And the proband 2 was his asymptomatic nephew who had a reduced PC activity of 27%. All the PC genes (PROC) and PLG genes were amplified by PCR with direct sequencing. Then these detected mutations were analyzed by conservation, bioinformatics, and model. Genetic analysis detected two compound heterozygous missense mutations: the proband 1 carried a p.Gly86Asp in PC and a p.Ala601Thr in PLG, whereas the proband 2 took two mutations of PC (p.Gly86Asp and p.Arg147Trp). All conservation, bioinformatics prediction, and model analysis results indicated that these mutations probably affected the structures and stabilities of the matching proteins. We speculated that the three mutations are responsible for the reduction of PC activity and PLG activity. Furthermore, the p.Gly86Asp of PC has been detected for the first time in the world.