The Organic Rankine Cycle (ORC) is an electricity generation system that uses organic fluid instead of water in the low temperature range. The Organic Rankine cycle using zeotropic working fluids has wide application potential. In this study, data mining (DM) model is used for performance analysis of organic Rankine cycle (ORC) using zeotropik working fluids R417A and R422D. Various DM models, including Linear Regression (LR), Multi-Layer Perceptron (MLP), M5 Rules, M5 Model Tree, Random Committee (RC), and Decision Tree (DT) models are used. The MLP model emerged as the most effective approach for predicting the thermal efficiency of both R417A and R422D. The MLP’s predicted results closely matched the actual results obtained from the thermodynamic model using Genetron software. The Root Mean Square Error (RMSE) for the thermal efficiency was exceptionally low, at 0.0002 for R417A and 0.0003 for R422D. Additionally, the R-squared (R2) values for thermal efficiency were very high, reaching 0.9999 for R417A and R422D. The findings demonstrate the effectiveness of the DM model for complex tasks like estimating ORC thermal efficiency. This approach empowers engineers with the ability to predict thermal efficiency in organic Rankine systems with high accuracy, speed, and ease.