An orthogonally designed experiment was conducted to investigate the effects of different N, P and K levels on plant growth and the uptake of Zn and Cd by hyperaccumulator Sedum plumbizincicola. The results showed that the addition of nitrogen fertilizer was the main factor in increasing plant biomass, and the highest dry weight (31.2 g/pot) occurred in the treatment of N2P1K0 (200 mg/kg N, 60 mg/kg P, no K), which was 3.15 times of the CK (N0P0K0). K application was the main factor in enhancing concentration and uptake of heavy metals, especially Cd by Sedum plumbizincicola. Cd concentration in shoot of the treatments of 160 mg/kg K was 28.1% higher than the treatments of no K addition, and the phytoextraction efficiency could be improved when low amount of P (60 mg/kg P) was applied. By comprehensively considering the biomass of Sedum plumbizincicola and the uptake amount of Zn and Cd, it was proposed that the best treatment was low N and P but high K (N1P1K2), and Zn and Cd phytoextraction rates in one season of Sedum plumbizincicola were 11.2 mg/kg and 0.12 mg/kg, respectively.