15 alkyl imidazoline surfactants with different structures were synthesized and their critical micelle concentration (CMC) and surface tension under the CMC (σcmc) in aqueous solution were measured at 298 K. 54 kinds of molecular structure descriptors were selected as independent variables and the quantitative structure-activity relationship (QSAR) between surface activities of alkyl imidazoline and molecular structure were built through the genetic function approximation (GFA) method. Experimental results showed that the maximum surface excess of alkyl imidazoline molecules at the gas-liquid interface increased and the area occupied by each surfactant molecule and the free energies of micellization ΔGm decreased with increasing carbon number (NC) of the hydrophobic chain or decreasing hydrophilicity of counterions, which resulted in a CMC and σcmc decrease, while the log CMC and NC had a linear relationship and a negative correlation. The GFA-QSAR model, which was generated by a training set composed of 13 kinds of alkyl imidazoline though GFA method regression analysis, was highly correlated with predicted values and experimental values of the CMC. The correlation coefficient R was 0.9991, which means high prediction accuracy. The prediction error of 2 kinds of alkyl imidazoline CMCs in the Validation Set that quantitatively analyzed the influence of the alkyl imidazoline molecular structure on the CMC was less than 4%.