Objective To fit the functional relation between Percentage Depth Dose and depth by Newton Interpolation. Methods After analyzing the data of Percentage Depth Dose from different manufacturers' linear accelerators, the average of Percentage Depth Dose with same depth was calculated, and then the average data was determined. The interval was set and the interpolation node was selected for simulating the cubic polynomial with PDD and depth. Results Comparing the calculated values by the function with the measured ones, the error was less than 1%. Conclusion The function simulated with Newton Interpolation is applicable in routine clinical radiotherapy and research.