AIM: To investigate the interaction between hepatitis C viruscore protein and translin protein and its role in thepathogenensis of hepatocellular carcinoma and lymphoma.METHODS: With the components of the yeast two hybridsystem 3, bait plasmids of HCV core the gene wasconstructed. After proving that hepatitis C virus core proteincould be firmly expressed in AH109 yeast strains, yeast two-hybrid screening was performed by mating AH109 with Y187that transformed with liver cDNA library plasmids - pACT2and then plated on quadrople dropout (QDO) medium andthen assayed for α-gal activity. Sequencing analysis of thegenes of library plasmids in yeast colonies that could growon QDO with α-gal activity was performed. The interactionbetween HCV core protein and the protein we obtained frompositive colony was further confirmed by repeating yeasttwo - hybrid analysis and coimmunoprecipitation in vitro.RESULTS: A gene from a positive colony was the gene oftranslin, a recombination hotspot binding protein. Theinteraction between HCV core protein and translin proteincould be proved not only in yeast, but also in vitro.CONCLUSION: The core protein of HCV can interact withtranslin protein. This can partly explain the molecularmechanism for hepatocellular carcinoma and lymphomacaused by HCV.