Herein we report a quinoline modified oxacalixarene architecture (HQOC) that shows chelation enhanced turn-on fluorescence response toward Al3+. The presence of hard carbonyl oxygen and quinoline nitrogen plays an important role in switching-on the system through coordinating with hard Al3+ ions. The photophysical of the probe HQOC toward aluminium were thoroughly investigated using various techniques including UV–vis spectroscopy, fluorescence and NMR spectroscopy. The sequential detection of Al3+ and picric acid is immensely significant in evaluating its presence in the human ecosystem. HQOC allowed the specific recognition and quantification of Al3+ and picric acid with the detection limits of 24.60 nM and 34.28 nM. The Density Functional Theory (DFT) calculations further provide insight into the mechanistic aspects and electronic transitions involved during sensing. Additionally, we extended the work toward several bio-analytical applications. The cytotoxicity of the synthesized complex was screened against Peripheral Blood Mononuclear Cells (PBMC) by MTT assay and subsequently cell imaging, DNA cleavage activity was also explored for amenable therapeutic needs.