Major allergic diseases are caused by an increased accumulation of eosinophils driven by interleukin 5 (IL-5). Chromenone analogues have been demonstrated as a promising scaffold for IL-5 inhibitors to control allergic diseases. Therefore, the molecular interaction of IL-5 inhibitors with biological targets is important for better drug discovery. In this study, we analysed in vitro data using 3D-QSAR (Quantitative Structure-Activity Relationships) modelling to find the IL-5 inhibitory activity and molecular interaction. The results of Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Field Similarity Indices (CoMSIA IB) revealed that the in vitro IL-5 inhibitory activity of these chromenone derivatives exhibited strong correlations with steric and electrostatic factors of the molecules (q2 =0.503, = 0.997, and = 0.989 for CoMFA standard model and q2 =0.623, = 0.973, and = 0.990 for CoMSIA model). 3D-QSAR field contour maps could be generated to identify the important structural features of chromenone analogues relevant to the IL-5 inhibitory activity.