Background Several risk factors, among other lifestyle factors, have been suggested for hand eczema (HE). Objectives To investigate a possible association between HE and lifestyle factors, including smoking, alcohol consumption, stress, body mass index (BMI), waist circumference, physical activity, diet, and amount of sleep in the Dutch general population. Methods Data from the large population-based LifeLines Cohort Study was used. Individuals with HE in the past year were identified by a cross-sectional questionnaire in 2020. At baseline, information on lifestyle factors was collected. Results In total 57 046 individuals were included in the present analysis. Smoking >= 8 cigarettes/day, and smoking >= 15 pack years showed a positive association with HE in the past year. In addition, chronic stress, a BMI >30 kg/m(2), and a waist circumference of >90 cm were positively associated with HE in the past year. Conclusions The current study indicates that lifestyle factors are associated with HE. Advice regarding lifestyle factors might contribute to enhance overall health, of which HE might possibly benefit in conjunction. Further studies should also focus on the association between lifestyle factors and the severity and prognosis of HE rather than on occurrence alone.