Thalassemia is one of the most common monogenic diseases, which seriously affects human growth and development, cardiovascular system, liver, etc. There is currently no effective cure for this disease, making screening for thalassemia particularly important. Herein, a self-powered portable device with high sensitivity and specificity for efficiently screening of low-level thalassemia is developed which is enabled with AuNPs/MoS2@C hollow nanorods and triple nucleic acid amplification technologies. It is noteworthy that AuNPs/MoS2@C electrode shows the advantages of high electrocatalytic activity, fast carrier migration rate and large specific surface area, which can significantly improve the stability and output signal of the platform. Using high-efficiency tetrahedral DNA as the probe, the target CD122 gene associated with thalassemia triggers a catalytic hairpin assembly reaction to achieve CD122 recycling while providing binding sites for subsequent hybridization chain reaction, greatly improving the detection accuracy and sensitivity of the device. A reliable electrochemical/colorimetric dual-mode assay for CD122 is then established, with a linear response range of 0.0001–100 pM for target concentration and open circuit voltage, and the detection limit is 78.7 aM (S/N = 3); a linear range of 0.0001–10000 pM for CD122 level and RGB Blue value, with a detection limit as low as 58.5 aM (S/N = 3). This method achieves ultra-sensitive and accurate detection of CD122, providing a new method for the rapid and accurate screening of thalassemia.