Hepatitis C is an important blood borne infection caused by hepatitis C virus (HCV). Chronic inflammationinduced by this viral infection and its role in carcinogenesis are well recognized. The treatment of HCV infectionhas developed enormously over recent years and is believed to be a good way for stopping of carcinogenesisprocess. Howevr, mutation of the virus is an important factor that can bring drug resistance. Presently, predictionof protein nanostructure and function is a great challenge in the proteomics and structural genomics era. Toidentify points which are vulnerable to mutation is a new trend to expand the knowledge at the genomic andproteomic levels Here, the author performed a bioinformatic analysis to determine positions that trend to complywith peptide motifs in the amino acid sequence of HCV protein kinase -eIF2-alpha phosphorylation homologydomain (PePHD). To identify weak linkage in HCV PePHD, a new bioinformatic tool, GlobPlot, was used. Positions2-7, 29-39, 53-57, 90-98, 123-133, 202-227, 324-355, 439-448 were identified as positions resistant to mutation.Some are already known and others are newly discovered. Based on this study, weak linkages in HCV PePHDcould be identified and can be good information for expectation of possible new mutations that can lead to failureof HCV therapy. In addition, the results from this study can be good information for further research on thediagnosis for mutants HCV and vaccine development.