This paper is focused on the effects of radio frequency (RF) heating on the relative activity of polyphenol oxidase (PPO), weight loss, texture, color, and microstructure of potatoes. The results showed that pure mushroom PPO was almost completely inactivated at 80 °C by RF heating. The relative activity of potato PPO reduced to less than 10% with increasing temperature (25-85 °C). Enzyme extract showed the lowest PPO relative activity at 85 °C after RF treatment, followed by the potato cuboids and mashed potato, about 0.19 ± 0.017%, 3.24 ± 0.19%, and 3.54 ± 0.04%, respectively. Circular dichroism analysis indicated that RF heating changed the secondary structure of PPO, as α-helix content decreased. Both electrode gap and temperature had significant effect (P < .05) on weight loss, color, and texture of the potato cuboids. Microstructure analysis showed the changes of potato cell and starch during RF heating.