A detailed study of the tautomeric properties, the conformations, and the mechanism behind the anti-cancer properties of 5-{[2-(4-methoxyphenyl)-1H-benzimidazol-1-yl]methyl}-4-ethyl-2,4-dihydro-3H-1,2,4-triazole-3-thione (1), 2-(4-chlorophenyl) (2), 2-phenyl (3), 2-(3,4-dibenzyloxyphenyl) (4), and 2-(4-methoxyphenyl); 4-[2-(piperidin-1-yl)ethyl] (5) has been conducted using density functional theory and molecular docking. The most stable states of all the structures are shown to be in the thione form. The scans of the compounds point out two conformers at PES, one of two conformers for molecule 1 corresponds to X-ray geometry, being the lowest energy state. Current molecules (1, 2, 3, and 5) have one inter-molecular hydrogen bond between NH atom of triazole ring and =O atom in residue ARG817 of the EGFR binding pocket, while compound 4 has different type inter-molecular hydrogen bond which is between N atom in benzimidazole ring and H atom of NH3 in residue LYS721. Off all hydrogen bonds, that of 5 is the strongest one with 2.26 A. Compound 4 has shown the best binding affinity with −10.0 kcal/mol. This compound is the most active compound regarding to the potential anti-cancer activity.