Hepatitis B virus (HBV) infection is a universal health problem and may result into acute, fulminant, chronic hepatitis liver cirrhosis, or hepatocellular carcinoma. Sequence for protein X of HBV was retrieved from Uniprot database. ProtParam from ExPAsy server was used to investigate the physicochemical properties of the protein. Homology modeling was carried out using Phyre2 server, and refinement studies were done with Galaxy web browser. Five models were generated and evaluated by ERRAT, ANOLEA, QMEAN6, and PROCHECK. Antigenicity of the protein was also evaluated by Chou & Fasman beta-turn prediction method. Five models were generated, and model 1 was having the greatest quality on the basis of the QMEAN6 score with 0367 ERRAT analysis, revealing the overall quality of 54054% whereas the initial model was having only 17730% quality. The mean force potential energy, as analyzed by ANOLEA, was better compared with the initial model. Stereochemical quality estimation by Procheck showed that the refined model 1 had a reliable structure, and was therefore submitted to the protein model database. Pyrx with Autodock vina was used to screen the compounds from Drug bank and Protein Data Bank to find the molecules that can bind to the active site between 1 to 142 amino acids. Ten compounds with highest negative energy were selected as lead molecules. Transactivation domain predicted by MOTIF program and 3D structure submitted to PMDB can be used to design new drugs against HBV protein X.