Disinfection of dentures and denture liners was desired for cross-contamination prevention and improved safety. Nonetheless, it has been discovered that these procedures impact the physical and mechanical features of denture liners.To assess the impact of different disinfection procedures on the tensile bond strength of an acrylic-based soft liner with CAD/CAM-based acrylic denture resin. Material and Methods: 25 specimens were collected and randomly divided into five groups (sodium hypochlorite, chlorohexidine, cleansing tablet, microwave, and control groups), following the daily disinfection protocol, the samples were stored at room temperature (23±2°C) in distilled water. After 30 days, the tensile bond strength was determined using universal testing equipment (Gester, China). The specimens were subjected to force by the machine at a steady crosshead speed of 5 mm/minute till the failure was recorded. The data were analyzed using statistics software (SPSS). Results: Showed that the control group had a higher mean value for bond strength, whereas the chlorhexidine group had a lower value. There was no significant difference between the control and cleansing tablet groups. However, they were significantly different from the microwave, CHX, and NaOCl groups. The NaOCl soft liner group is significantly different from all the other groups. No significant difference is found between microwave and CHX disinfected liner groups. Conclusion: The tensile bond strength of all disinfected soft liners decreased as compared with the control, which was not significant with the protefix tab but significant with the NaOCl, CHX, and microwave groups.