Support vector machines have a wide use for the prediction problems in life sciences. It has been shown to offer more generalisation ability in input–output mapping. However, the performance of predictive models is often negatively influenced due to the complex, high-dimensional, and non-linear nature of the post-genome data. Soft computing methods can be used to model such non-linear systems. Fuzzy systems are one of the widely used methods of soft computing that model uncertainties. It is formed of interpretable rules aiding one to gain insight into applied model. This study is therefore concerned to provide more interpretable and efficient biological model with the development of a hybrid method that integrates the fuzzy system and support vector regression. In order to demonstrate the robustness of this new hybrid method, it is applied to the prediction of peptide binding affinity being one of the most challenging problems in the post-genomic era due to diversity in peptide families and complexity and high-dimensionality in the characteristic features of the peptides. Having used four different case studies, this hybrid predictive model has yielded the highest predictive power in allthe four cases and achieved an improvement of as much as 34% compared to the results presented in the literature. Availability: Matlab scripts are available at https://github.com/sekerbigdatalab/tsksvr.