Recent studies have implicated the role of the Notch pathway in keratinocyte carcinomas (KCs). Notch signaling is often upregulated in basal cell carcinoma (BCC) but downregulated in squamous cell carcinoma (SCC). Hidradenitis suppurativa (HS) is an inflammatory disorder of the apocrine glands whose pathogenesis has also been associated with downregulation of Notch signaling. Given the role of Notch in the pathogenesis of HS and KCs, we hypothesized that HS patients could be at decreased risk for BCC and increased risk for SCC. To test our hypothesis, we examined the association between HS and KC risk by comparing the incidence of BCC and SCC in HS patients to controls (patients with acne vulgaris, an inflammatory disorder of pilosebaceous glands that is not known to involve the Notch pathway). Using an age, sex, and race matched 1:2 case-control study design, we derived KC outcomes and covariates through chart review of an institutional database (Partners Healthcare, 2000-2019) and determined incident BCC and SCC risk by performing multivariate logistic regression adjusted for disease duration, BMI, smoking, immunosuppression, and number of dermatology visits. The study population consisted of 13,812 patients (4,604 HS and 9,208 acne patients), of which 59% were white, 74.7% female, and mean (SD) age was 43.7 (15.4) years. Adjusted odds ratio (OR) for incident BCC risk in HS was OR 0.51 (95% CI 0.37-0.71, P<0.001) whereas adjusted OR for incident SCC risk was 0.79 (95% CI 0.54-1.17, P=0.238). There were no statistical differences in age, gender, and race among those who developed BCC or SCC between groups (all P>0.05). Our results suggest that HS patients have reduced risk of BCC, and similar risk of SCC, compared with controls (acne patients). Further studies are needed to investigate whether decreased Notch signaling in HS patients plays a protective role in BCC tumorigenesis or whether inflammation of the pilosebaceous unit in acne affects follicular bulge cells to increase risk of BCCs.