Monocyclic aromatic hydrocarbons (MAHs) are being used as individual chemicals or as in mixtures of two or more chemicals in several industrial and household processes across the world. Among MAHs, the most common chemicals are benzene, toluene and xylene, and they are also known as volatile organic compounds (VOCs), among them benzene categorised as highly toxic chemical and also listed as human carcinogen. Benzene, toluene and xylene cause cytotoxicity to a nontarget organism-like Drosophila melanogaster as an individual (benzene or toluene or xylene)/in mixture (benzene-toluene-xylene or benzene-toluene or benzene-xylene). In this chapter, several cellular, biochemical and molecular approaches were used to evaluate cellular toxicity due to MAHs like benzene, toluene and xylene using Drosophila melanogaster as an alternative to animal. We also judged variable cytotoxicity patterns of MAHs when they are exposed individually or in a mixture of two/three chemicals. An antagonistic effect of xylene and toluene on benzene toxicity and additive/synergistic effect of xylene on toluene-induced toxicity were evident in Drosophila. This study shows that co-exposure of benzene-toluene-xylene causes reduced cellular and organismal toxicity as compared to individual test chemical on Drosophila melanogaster.