To describe the effectiveness and tolerability of low-dose interleukin (IL)-2 in treating patients with chronic spontaneous urticaria (CSU) refractory to H1-antihistamines. This retrospective study included CSU patients who received treatment with at least one cycle of IL-2, injected intramuscularly at a dose of 1.0 million international units daily for 7 consecutive days, after failing treatment with H1-antihistamines. Patients were followed up for ≥12 weeks. Of the 15 patients, 7 (46.7%) and 11 (73.3%) achieved complete response at Week 2 and Week 12, respectively. The mean change of urticaria control test (UCT) and weekly urticaria activity score (UAS7) from baseline was 6.6 (95% CI, 4.2 to 8.9) and − 16.9 (95% CI, −24.0 to −9.8), respectively, at Week 12. Local injection-site reactions were the most common adverse events. No serious adverse events were reported. Low-dose IL-2 treatment improves symptoms and disease control for CSU patients refractory to H1-antihistamines. •Chronic spontaneous urticaria refractory to H1-antihistamines has unmet needs.•Low-dose interleukin-2 achieves quick response in chronic spontaneous urticaria.•12 weeks after low-dose interleukin-2, 73.3% of patients gained complete response.•Distinct patterns of response to treatment between ASST(+) and ASST(−) patients.•Low-dose interleukin-2 can be a novel treatment for chronic spontaneous urticaria.