In this study, expression of mature Hepatitis C virus core protein (HCVC173), consistent with a viral isotype isolated in Iran, was studied in E. coli. The 20 kDa- HCVC173 protein was expressed while it contains 18% of total expressed proteins in which a part was partially soluble but the main part was expressed in insoluble inclusion body. However, the produced inclusion body has not shown the expected purity and HCVC173 has been aggregated with the host proteins. Moreover, during refolding of insoluble HCVC173, notable aggregation of the protein was undesirable phenomena. Intramolecular evaluation of target expressed protein predicted two irregularity area in the HCVC173 which may aggregate the expressed protein. Consequently, HCVC173 has the features of the intrinsically unstructured proteins. This character may justify its aggregation during refolding. Moreover, the approach presented in this paper is an alternative solution to overcome the expression limitation of mature form of the HCVC protein.