(1)Background:Phenotype prediction is a pivotal task in genetics in order to identify how genetic factors contribute to phenotypic differences. This field has seen extensive research, with numerous methods proposed for predicting phenotypes. Nevertheless, the intricate relationship between genotypes and complex phenotypes, including common diseases, has resulted in an ongoing challenge to accurately decipher the genetic contribution. (2)Results:In this study, we propose a novel feature selection framework for phenotype prediction utilizing a genetic algorithm (FSF-GA) that effectively reduces the feature space to identify genotypes contributing to phenotype prediction. We provide a comprehensive vignette of our method and conduct extensive experiments using a widely used yeast dataset. (3)Conclusions:Our experimental results show that our proposed FSF-GA method delivers comparable phenotype prediction performance as compared to baseline methods, while providing features selected for predicting phenotypes. These selected feature sets can be used to interpret the underlying genetic architecture that contributes to phenotypic variation.