In the field of biology, researchers need to compare genes or gene products using semantic similarity measures (SSM). Continuous data growth and diversity in data characteristics comprise what is called big data; current biological SSMs cannot handle big data. Therefore, these measures need the ability to control the size of big data. We used parallel and distributed processing by splitting data into multiple partitions and applied SSM measures to each partition; this approach helped manage big data scalability and computational problems. Our solution involves three steps: split gene ontology (GO), data clustering, and semantic similarity calculation. To test this method, split GO and data clustering algorithms were defined and assessed for performance in the first two steps. Three of the best SSMs in biology [Resnik, Shortest Semantic Differentiation Distance (SSDD), and SORA] are enhanced by introducing threaded parallel processing, which is used in the third step. Our results demonstrate that introducing threads in SSMs reduced the time of calculating semantic similarity between gene pairs and improved performance of the three SSMs. Average time was reduced by 24.51% for Resnik, 22.93%, for SSDD, and 33.68% for SORA. Total time was reduced by 8.88% for Resnik, 23.14% for SSDD, and 39.27% for SORA. Using these threaded measures in the distributed system, combined with using split GO and data clustering algorithms to split input data based on their similarity, reduced the average time more than did the approach of equally dividing input data. Time reduction increased with increasing number of splits. Time reduction percentage was 24.1%, 39.2%, and 66.6% for Threaded SSDD; 33.0%, 78.2%, and 93.1% for Threaded SORA in the case of 2, 3, and 4 slaves, respectively; and 92.04% for Threaded Resnik in the case of four slaves.