Prediction and classification of diseases are essential in medical science, as it attempts to immune the spread of the disease and discover the infected regions from the early stages. Machine learning (ML) approaches are commonly used for predicting and classifying diseases that are precisely utilized as an efficient tool for doctors and specialists. This paper proposes a prediction framework based on ML approaches to predict Hepatitis C Virus among healthcare workers in Egypt. We utilized real-world data from the National Liver Institute, founded at Menoufiya University (Menoufiya, Egypt). The collected dataset consists of 859 patients with 12 different features. To ensure the robustness and reliability of the proposed framework, we performed two scenarios: the first without feature selection and the second after the features are selected based on sequential forward selection (SFS). Furthermore, the feature subset selected based on the generated features from SFS is evaluated. Naïve Bayes, random forest (RF), K-nearest neighbor, and logistic regression are utilized as induction algorithms and classifiers for model evaluation. Then, the effect of parameter tuning on learning techniques is measured. The experimental results indicated that the proposed framework achieved higher accuracies after SFS selection than without feature selection. Moreover, the RF classifier achieved 94.06% accuracy with a minimum learning elapsed time of 0.54 s. Finally, after adjusting the hyperparameter values of the RF classifier, the classification accuracy is improved to 94.88% using only four features.