Despite much progress in clinical and basic research on hepatitis C virus (HCV), interactions between HCV proteins and human proteins is not fully understood. HCV envelope proteins have many cellular targets in human proteins and affect several biological functions. From the analysis of known interactions between HCV E2 envelope proteins and human proteins, we identified a binding motif A-x(3,5)-A-x(0,2)-V-V-x[DKR]-[DS]-[AV]-[ENS]-[DEGN] in all interacting human proteins. This binding motif is essential to the interactions with HCV envelope proteins. We also found several sequence patterns in HCV E2 proteins. The binding motif and sequence patterns found in our study would be helpful in better understanding of interaction mechanisms and in design of new drugs to combat the disease.