The aim of the study was to investigate the efficacy and safety of halometasone cream to treat chronic generalized eczema and the effects of halometasone cream on serum cortisol (COR) levels. Sixty consecutive outpatients diagnosed with chronic generalized eczema between January and April 2017 were included and divided into groups A, B, and C with a lesion area of 30%-40%, 41%-50%, and 51%-60%, respectively. Groups A, B, and C were treated with halometasone cream with a daily dose of 15g, 20g, and 30g for 7-14 days, respectively. Ten patients were randomly selected from each group for serum COR measurement at days 0, 7, and 14. On day 14, group B had significantly higher cure rate (47.1%) than groups A (17.9%) and C (13.3%) and significantly higher effectiveness rate (82.4%) than group C (40.0%) (all P < 0.05). Serum COR levels were not affected in group A but were reduced significantly in groups B and C on days 7 and 14 (all P < 0.05). No adverse reaction was observed. Halometasone cream appeared to relieve chronic generalized eczema effectively and safely. High dosage (>= 20 g daily for 14 days) may temporarily reduce endogenous COR production substantially, although it may be more effective.