A QSAR study was performed on ninety eight substituted biphenyl analogues of 2-nitroimidazo-[2, 1-b] [1, 3]- oxazines as antitubercular agents to explore the importance of topological, thermodynamic, spatial and physicochemical properties of the molecules towards the antitubercular activity. Genetic function approximation (GFA) was used as the chemometric tool for the study. The study shows that ortho and meta linked attachments of the biphenyl analogs to 2- nitroimidazo-[2, 1-b] [1, 3]-oxazines are detrimental for the antitubercular activity. Hydrophobicity, branching and presence of electronegative atoms enhance the activity. Based on the rm 2 (overall) criterion, which considers both internal validation and external validation, a GFA model with spatial, thermodynamic and topological descriptors appears to be the best model (rm 2 (overall) =0.556).