HSP gene polymorphism has been widely studied across the globe and particularly with reference to various liver diseases and HCC. Data pertaining to HSP gene polymorphism is lacking from NE India region and there are lacunae of information at the proteomic and bioinformatics level. NE region of India is known for its high incidence of cancer cases. The current study was designed to study the polymorphism of HSP genes in different liver disease cases from Guwahati, India and to predict 3D structure of the proteins from the studied genes by using different bioinformatics tools as well as calculating different physio-chemical information of those studied proteins. The DNA extraction was done followed by PCR amplification and RFLP. EMBOSS Transeq tool and I- TASSER SERVER were used to model the proteins of interest. The results showed that HSPA1B and HSPA1L polymorphisms are significantly associated with advanced stages of liver diseases. Stable protein 2D and 3D models were successfully proposed in this study. The current study highlights the importance of studying cancer critical gene and the need of bioinformatics softwares to generate data