Acquired reactive proliferating collagen (ARPC), usually associated with systemic diseases, is a rare skin disease characterized by the elimination of altered dermal collagen through the epidermis. Here, we report two cases of ARPC in maintenance hemodialysis patients, one of which is combined with type 2 diabetes, chronic renal failure, and hypertension and the other is combined with chronic renal failure and hypothyroidism. Two patients were treated with oral thalidomide and ebastine, local application of fluticasone propionate cream, and enhanced dialysis. After treatment, the itching and the rash significantly improved. We report for the first time that ARPC in patients with hemodialysis could be improved by oral thalidomide and antihistamines and local application of steroid. This report provides reference for guiding the understanding of ARPC and the new treatment of ARPC in hemodialysis patients.