In the last decade, many proteins or large segments of proteins without well-structured three-dimensional folding have been identified. Disordered regions can be highly conserved between species and contrary to the traditional view that the function of a protein is closely linked to its three-dimensional structure, disordered regions are often functional. The disordered segments are able to fold under binding to their biological targets or constitute flexible linkers that are important to the assembly of macromolecular arrays. The Hepatitis C virus core protein has a random structure in the absence of the C-terminal. This random structure has been shown to be responsible for modulation of several cellular processes or induction of hepatocellular carcinoma. Here we utilized fluorescence and circular dichroism spectroscopy to investigate the conformational changes of this protein in the presence of several ligands and different treatments, and electron microscopy to analyze nucleocapsid-like particles formation. We show that the HCV core protein can adopt an intermediate structure in the presence of the probe bis-8-anilinonaphthalene-1-sulfonate (bis-ANS), butanol, trifluorethanol (TFE), micelles and monomers of the sodium dodecil sulphate (SDS), high temperatures and different pH. Some ligands, such as DNA and RNA, were able to cause changes on the secondary structure of this protein. Besides the truncated core protein was be able to form virus-like particles. In comparison, we are starting the study of the native core protein that contains the C-terminal region. Our data showed that the HCV core protein underwent changes on its secondary structure in the presence of such ligands and physical conditions, what can mimicry the physiological environment where it binds to different targets. Financial Support: CNPq, CAPES, Pronex, FAPERJ and FUJB/UFRJ.