In this present study, the crystal structure of 2,2,2-trifluoroacetophenone (TFAP) is determined using in situ cryocrystallization techniques. The main objective of this work is to study its crystal packing associated with the various intermolecular interactions, along with a detailed comparison with the features of substituted analogs. It is interesting to note how the chemical substitution of different functional groups influences the crystal packing, the electronic environment of the molecule and the nature of the various intermolecular interactions.