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Hidradenitis suppurativa (HS) places a significant burden on the health-related quality of life (HRQOL) of patients, many of whom have depression. Resilience can play a role in mitigating the negative stressors, such as the symptoms of HS, on patients’ mental health.To investigate the correlation among resilience, depression, and HRQOL for patients with HS.This cross-sectional survey study of 154 patients from 2 referral centers in the United States and in Denmark was conducted from June 1, 2016, to March 31, 2017. Patients were considered eligible if they were 18 years or older and had a visit for HS at 1 of the 2 referral centers in the past 2 years (from January 1, 2014, through December 31, 2016). Patients were excluded if they declined to participate, could not read or write in English or Danish, or had a cognitive disability that would preclude their understanding of the survey questions.The survey instrument included 4 questionnaires: (1) a sociodemographic and clinical characteristics questionnaire, (2) the Brief Resilient Coping Scale, (3) the Hospital Anxiety and Depression Scale, and (4) the Dermatology Life Quality Index. The main outcome of interest was the HRQOL as measured by the Dermatology Life Quality Index.All 154 patients submitted a completed survey. The mean (SD) age of the participants was 40.93 (13.5) years; most participants were women (130 [84.4%]), and most participants self-identified as white (139 [90.2%]). The rate of depression among the patients in this study was comparable to those reported in previous studies; 55 patients (35.7%) were classified as having depression, and 32 patients (20.8%) had borderline depressive symptoms. Patient-rated HS severity and the depression score each independently estimated 27% and 10% of variation in HRQOL, respectively. The interaction term for resilience and depression was significant, indicating that resilience moderates depression. Analysis of the mediation effects of resilience was not significant, indicating that resilience did not mediate the association between depressive symptoms and HRQOL. The resilience score was significantly associated with depressive symptoms (regression coefficient a = −0.21; P < .001), and the depressive symptoms score (c = 0.637; P < .001) was significantly associated with lower HRQOL (c′ = 0.644; P < .001). However, both the direct association (b = 0.033; P = .86) and the indirect association (a × b = 0.007; P = .87) of resilience with HRQOL were not significant.Patients with higher resilience levels experienced a smaller decrease in HRQOL as depressive symptoms increased. Because the findings suggest that resilience can be taught, there is an opportunity to develop a resiliency training program and investigate its role in stress levels and depressive symptoms, as well as in HRQOL and disease activity.