An efficient electrochemical sensor was presented for lead cation detection using a DNA functionalized iron-porphyrinic metal-organic framework (GR-5/(Fe-P)n-MOF) as a probe. The newly designed probe showed both the recognition behavior of GR-5 to Pb(2+) with high selectivity and the excellent mimic peroxidase performance of (Fe-P)n-MOF. In the presence of Pb(2+), GR-5 could be specifically cleaved at the ribonucleotide (rA) site, which produced the short (Fe-P)n-MOF-linked oligonucleotide fragment to hybridize with hairpin DNA immobilized on the surface of screen-printed carbon electrode (SPCE). Because of the mimic peroxidase property of (Fe-P)n-MOF, enzymatically amplified electrochemical signal was obtained to offer the sensitive detection of Pb(2+) ranging from 0.05 to 200 nM with a detection limit of 0.034 nM. In addition, benefiting from the Pb(2+)-dependent GR-5, the proposed assay could selectively detect Pb(2+) in the presence of other metal ions. The SPCE based electrochemical sensor along with the GR-5/(Fe-P)n-MOF probe exhibited the advantages of low-cost, simple fabrication, high sensitivity and selectivity, providing potential application of on-site and real-time Pb(2+) detection in complex media.