Heavy metal pollution is currently an increasing threat to the ecological environment, and the development of novel absorbents with remarkable adsorption performance and cost-effectiveness are highly desired. In this study, a cassava starch-based Pb(II)-imprinted thermo-responsive hydrogel (CPIT) had been prepared by using cassava starch as the bio-substrate, N-isopropyl acrylamide (NIPAM) as the thermo-responsive monomer, and Pb(II) as the template ions. Later, a variety of modern techniques including FTIR, DSC, SEM, and TGA were employed to comprehensively analyze the characteristic functional groups, thermo-responsibility, morphology, and thermal stability of CPIT. The obtained material exhibited superior performance in adsorption of Pb(II) and its maximum adsorption capacity was high—up to 114.6 mg/g under optimized conditions. Notably, the subsequent desorption (regeneration) process was fairly convenient by simply rinsing with cold deionized water and the highest desorption efficiency could be achieved as 93.8%. More importantly, the adsorption capacity of regenerated CPIT still maintained 88.2% of the value of starting material even after 10 recyclings. In addition, the excellence of CPIT in selective adsorption of Pb(II) should also be highlighted as its superior adsorption ability (97.9 mg/g) over the other seven interfering metal ions.