The next-generation biosensing tools based on CRISPR-Cas have revolutionized molecular detection. A number of CRISPR-Cas-based biosensors have been reported for the detection of nucleic acid targets. The establishment of efficient methods for nonnucleic acid target detection would further broaden the scope of this technique, but up to now, the concerning research is limited. In the current study, we reported a versatile biosensing platform for nonnucleic acid called SMART-Cas12a (Small Molecule Aptamer Regulated Test using CRISPR-Cas12a). Simply, hybridization chain reaction (HCR) cascade signal amplification was first trigged by functional nucleic acid (aptamer) through target binding. Then the CRISPR-Cas system was integrated to recognize the amplified products followed by the activation of the trans-cleavage. As such, the target can be ingeniously converted to nucleic acid signals and then fluorescent signals that can be readily visualized and analyzed by a customized 3D-printed visualizer with the help of a homemade app-enabled smartphone. Adenosine triphosphate (ATP) was selected as a model target, and under the optimized conditions, we achieved fine analytical performance with a linear range from 0.1 to 750 μM and a detection limit (LOD) of 1.0 nM. The satisfactory selectivity and recoveries that we have obtained further demonstrated this method suitable for a complex sample environment. The sample-to-answer time was less than 100 min. Our work not only expanded the reach of the CRISPR-Cas system in biosensing but also provided a prototype method that can be generalized for detecting a wider range of analytes with desirable adaptability, sensitivity, specificity, and on-site capability.