Background: Denture base material that has been widely use in dentistry is acrylic resin. However, the resin acrylic denture base often breaks. So researchers have been develop new denture base material made from thermoplastic nylon. But, there is not clarified design (include the optimum thickness) of the thermoplastic nylon from the scientific point of view yet. The mechanical properties of the denture base is have good flexural strength, as it represents mastication movements. Objective: To know the differences of thermoplastic nylon’s flexural strength at thickness 1 mm, 1.5 mm, 2 mm, and 2.5 mm. Material and method: This study is a laboratory experimental study. Samples used in this study are 16 plates of thermoplastic nylon which were divided into 4 groups of thickness (1 mm, 1.5 mm, 2 mm, and 2.5 mm). The thermoplastic nylon plate was tested its flexural strength. Result: One Way Anova test of flexural strength, shows the p value is 0.016 (p <0.05), it means there is a significant difference of thermoplastic nylon’s flexural strength to its thickness. The highest mean of flexural strength is at 1 mm, and for the lowest flexural strength is at 2.5 mm. Conclusion: There is a difference in flexural strength of thermoplastic nylon material at thickness 1 mm, 1.5 mm, 2 mm, and 2.5 mm. The thicker thermoplastic nylon plate, the maximum forces of flexural tend to increase, but the flexural strength tend to decrease.