Nitro-compounds are widely used in medicine, agriculture and industry. Their toxicity issues attract more and more attention. There are a lot of factors influncing toxicity, and the degrees are different from one another. Some physical properties of compounds, such as the surface properties, may play crucial roles in the toxicity of these compounds. Twenty seven parameters of twenty eight nitro-compounds, including molecular size related parameters, molecular surface electrostatic potential based parameters, solubility parameters, molecular cohesive energies, surface tensions, dielectric constants and Mulliken charges of nitro groups, were considered to correlate with toxicity (semi-lethal dose, LD50) of the nitro-compounds. Fourteen parameters with higher correlation coefficients were... selected to join in the modelling process of heredity and variation (genetic function approximation), further screening toxicity related parameters, the screened parameters are molecular surface electrostatic potentials based σ + 2 , σ − 2 , νσ2 tot , + AS , VS , Log POW, and nitro group’s Mulliken charges NO2 q . Building the linear relation between toxicity and these screened parameters, and quantitatively studying the toxicity of nitro-compounds, this work may help us evaluate health risks and approach the toxicology of nitro-compouds.