Inspired by the natural enzyme cascade reaction, a multiple DNAzyme cascade platform is engineered to imitate the intracellular process of signal transduction and signal amplification. In this design, when particular stimuli appear, an activated upstream DNAzyme will cleave a well-designed intermediary S1, releasing a downstream DNAzyme that can cleave the reporter substrate S2 to output signals. Thus, the signal is passed from the upstream DNAzyme to the downstream DNAzyme through a well-designed intermediary, accomplishing signal transduction and signal amplification. According to the experimental results, the DNAzyme cascades are capable of improving sensitivity for bioassays compared with that for single DNAzyme-based biocatalysis, which holds promise for potential applications, such as biomolecular computing, logic circuits and precision medicine.