A novel signal amplification strategy for ultrasensitive detection of alpha-fetoprotein (AFP) based on the synergistic catalysis of hollow Pt nanochains (HPtNCs) and hemoglobin (Hb) with DNA-based hybridization chain reaction (HCR) has been reported in this work. Firstly, numerous biocatalysts of Hb and redox probes of thionine (Thi) were carried onto the double-stranded DNA polymers based on HCR with high affinity. It is worth pointing out that HCR could effective immobilize Hb and Tin under mild conditions maintaining the Hb's three-dimensional structure and avoiding the leakage of Tin. Significantly, the electrochemical signal was greatly enhanced by the synergistic catalysis of HPtNCs and Hb. With a sandwich-type immunoreaction, the linear dynamic range of AFP by differential pulse voltammetry was determined to be from 0.1 pg mL(-1) to 50 ng mL(-1) with the detection limit of 0.03 pg mL(-1) (S/N = 3). (C) 2013 The Electrochemical Society.