Currently, sensitive detection of microRNA (miRNA) in clinical diagnosis remains a challenge consideration of its extremely similar sequences and low concentration characteristics. In this work, a signal-enhanced biosensor constructed for ultra-sensitive miRNA detection based on two-dimensional (2D) transition metal sulfide materials and target induced -DNAzyme cycle and exonuclide-assisted cascade signal amplification strategy. As expected, miRNA-21 concentration has a good linear relationship with open circuit voltage of self-powered biosensor in the range of 1 fM-100 pM, and the detection limit is low as 0.03 fM. The results indicate that 2D materials have great potential in the construction of electrochemical sensors due to their large active surface area, high electron mobility and excellent electrocatalytic performance. In addition, the DNAzyme triggerd by chain substitution reaction can specifically identify the target and amplify the detection signal cyclically. Finally, the self-powered sensing platform with commercial chips, ensuring stable performance and minimal signal fluctuations during long-term continuous monitoring, enabling portable and real-time target monitoring.