In this study, a general approach is proposed that predicts the toxicological effects, to Photobacterium phosphoreum, of cyanogenic toxicants in combination with aldehydes. Forty binary mixtures containing an aldehyde and a cyanogenic toxicant were examined. The observed results indicate that the toxicological joint effects are different (additive, synergistic, or antagonistic) from each other, and the differences depend on chemical–chemical interactions between the cyanogenic toxicants and the aldehydes. Analysis of the chemical–chemical interactions reveals that there are two characteristics of individual chemicals that contribute to the joint effects: one is the charge of the carbon atom in the CHO group of aldehydes and the other is the charge of the carbon atom (C*) in the carbochain of cyanogenic toxicants. Based on these two contributors to toxicity, a quantitative structure-activity relationship (QSAR) model can be derived, namely M=0.367−0.811σp−6.704 C* where r2=0.868, SE=0.232, F=121.769, P=0.000, M is the sum of toxic units; σp is the Hammett Constant and is used to evaluate the charge of the carbon atom in the CHO of aldehydes; C* is the charge of the carbon atom in the carbochain of cyanogenic toxicants. Application of this model to the eight other related mixtures demonstrates the consistency between the predicted and observed toxicities, with r2=0.888, SE=0.223, F=45.562 at P=0.000. This prediction capability convinces us that the QSAR model provides a general approach to prediction of the joint toxicological joint effects of cyanogenic toxicants and aldehydes to Photobacterium phosphoreum.