To improve the soil fertility and tobacco growth in red soil areas for its strong soil acidity, low available nutrient content and poor air permeability, the soil physicochemical properties and tobacco growth with the application of magnesium sulfate and seaweed residue were investigated. A pot experiment with 6 treatments was conducted, i.e., CK: Control, without magnesium and seaweed residue, MS: Single application of 0.375 g magnesium sulfate per 1 kg soil, SF: Single application of seaweed residue 50 g per 1 kg soil, C1: Application of 0.375 g magnesium sulfate + 50 g seaweed residue per 1 kg soil, C2: Application of 0.563 g magnesium sulfate +75 g seaweed residue per 1 kg soil, C3: Application of 0.75 g magnesium sulfate +100 g seaweed residue per 1 kg soil. The effects of seaweed residue and magnesium on soil pH, organic carbon, mineral nutrient content, soil bulk density, and porosity, agronomic characteristics of tobacco and mineral nutrient contents of tobacco leaves were analyzed. The results showed that with the application of magnesium sulfate, seaweed residue alone or magnesium sulfate with seaweed residue, the agronomic traits, such as plant height, stem diameter, leaves of tobacco and biomass were significantly improved. Meanwhile, the contents of P and Mg in the tobacco leaves were significantly increased under the application of magnesium sulfate only. In addition, the contents of P, K and Mg in the tobacco leaves were also significantly higher in the application of seaweed residue alone or combined with magnesium sulfate. Compared with CK, soil pH of C3 treatment was significantly increased by 0.38 units, and the contents of alkaline - N, available - P, available- K, exchangeable - Ca and exchangeable - Mg were increased by 42.85%, 60.01%, 33.73%, 253.02% and 689.07% respectively. Soil organic carbon content of C1, C2 and C3 treatments increased by 212.9%, 385.7% and 540.7% than that of CK, respectively. The soil pH and soil organic carbon content were increased significantly with magnesium sulfate and seaweed residue application. The contents of available phosphorus, available potassium, exchangeable calcium and magnesium in soil were significantly increased by applying seaweed residue alone or in combination with magnesium. The application of seaweed residue alone or in combination with magnesium could significantly reduce soil bulk density and increase total soil porosity. Compared with CK, C3 treatment significantly reduced soil bulk density by 9.78%, and increased total porosity by 8.87%. It suggests that the growth of tobacco and physicochemical properties of red soil could be significantly improved by application with seaweed residue.