This study was conducted through orthogonal regression of field experiment by taking filled flue-cured tobacco variety "Longjiang 911" as the test materials, the regression effect of model was established between Nitrogen, Phosphorus and Potassium (NPK) fertilizers and flue-cured tobacco production. The various factors and interactions were analyzed, the contribution ratios and abundance/deficiency index of soil fertility were calculated and the Northeast Flue-cured Tobacco optimal fertilization program was established. The results showed that: production increased with the increase of nitrogen; production increased and then decreased with the increase of potassium; but phosphorus effect on tobacco production was not obvious; the synergistic and antagonistic effects between nitrogen and phosphorus, nitrogen and potassium, phosphorus and potassium were shown in the lower and higher range, respectively. The optimal fertilization model for the basis of the proposed tobacco fertilizer was: pure N 40.08 - 52.49 kg/hm2, P2O5 36.19 - 62.19 kg/hm2 , K2O 70.73 - 114.41 kg/hm2.