BACKGROUND: Asthma is a heterogeneous disease, which usually associated with chronic airway inflammation. The anti-heat shock protein (anti-HSP) 70 is a novel risk factor for asthma. The aim of the present study was to survey the effect of saffron supplementation on anti-HSP70, high-sensitivity C-reactive protein (hs-CRP) and spirometry test in patients with allergic asthma. BASIC PROCEDURES: In this clinical trial, patients (N = 80, 32 women and 48 men, 18-65 years old) with mild and moderate allergic asthma were randomized into two groups: a group of patients who received two capsules of saffron (100 mg/d) and a control group who received two capsules of placebo for 8 weeks. Anti-HSP70, hs-CRP and spirometry test were determined in patients before (week 0) and after (week 8) intervention. SPSS software (version 16.0; Inc, Chicago, IL) was used for data analysis. MAIN FINDINGS: Saffron in comparison with placebo significantly reduced the hs-CRP (p < 0.001) and anti-HSP70 (p < 0.001) concentrations. In spirometry test, forced expiratory volume in first second(FEV1), forced vital capacity (FVC), FEV1/FVC ratio and forced expiratory flow 25-75%.(FEF 25-75) increased significantly in saffron in comparison to placebo group (p < 0.05). PRINCIPAL CONCLUSIONS: Results of the present study suggested that saffron supplementation in patients with allergic asthma decreased significantly anti-HSPs 70 and hs-CRP and also improved some spirometry test factors.