This study aimed to determine the mediating role of emotion regulation difficulties in the correlation between mindfulness and psychological resilience. This study was conducted with a total of 119 patients diagnosed with major depression. Data were collected with Personal Information Form, Mindfulness Scale, Emotion Regulation Difficulties Scale, and Psychological Resilience Scale. The study participants reported moderate levels of mindfulness and emotion regulation difficulties, and above-average levels of psychological resilience. It was found that there was a moderately negative correlation between mindfulness and emotion regulation difficulties (r = −0.553, p