A Protein Data Bank study was conducted to check the role of C-halogen(X)…pi interactions (X = F, Cl, Br, I) in nucleic acids. The presence of halogens can be attributed to not only the modified residues of the nucleic acid but also the ones associated with the ligand. The study reports the presence of bromine amongst modified residues of the nucleic acid being the maximum than any other halogens. It is important to consider these interactions as they seem to be responsible for increasing the affinity of the ligand to the biomolecule concerned. The role of halogen-pi interactions becomes important to be assessed in orderto design halogenated ligands that will certainly be more effective in increasing the binding of the corresponding ligand to the target nucleic acid. The study attempts at listing the halogens that are prominent in the existing nucleic acid and ligand interactions which are deposited in the PDB. Inter-atomic interactions based on C-X…pi were analyzed to be found in several PDB IDs and similar ligand halogenation can be carried out to effectively increase binding affinity of halogenated ligands to nucleic acid based targets in case of severaldiseases.