Perfluorooctanoic acid (PFOA) is used in a variety of industries and is highly persistent in the environment, with potential human health risks. Photocatalysis has been extensively used for the decomposition of various organic pollutants, yet its simulation and modeling are challenging. This research aimed to establish different machine learning (ML) algorithms which can simulate and predict the photocatalytic degradation of PFOA. The published results were used to estimate and predict the photocatalytic degradation of PFOA. Statistical criteria including the coefficient of determination (R2), mean absolute error (MAE), and mean squared error (MSE) were considered in assessing the best method of modeling. Among the seven ML algorithms pre-screened, Adaptive Boosting (AdaBoost), Gradient Boosting Machine (GBM), and Random Forest (RF) showed the best performance and were chosen for deep modeling and analysis. Grid search was used to optimize the models developed by AdaBoost, GBM, and RF; and permutation variable importance (PVI) was used to analyze the relative importance of different variables. Based on the modeling results, GBM model (R2 = 0.878, MSE = 106.660, MAE = 6.009) and RF model (R2 = 0.867, MSE = 107.500, MAE = 6.796) showed superior performances compared with AdaBoost model (R2 = 0.574, MSE = 388.369, MAE = 16.480). Furthermore, the PVI results suggested that the GBM model provided the best outcome, with the light irradiation time, type of catalyst, dosage of catalyst, solution pH, irradiation intensity, initial PFOA concentration, oxidizing agents (peroxymonosulfate, ammonium persulfate, and sodium persulfate), irradiation wavelength, and solution temperature as the most important process variables in decreasing order. [ABSTRACT FROM AUTHOR]