Abstract： A 54-year-old female was born with erythema,scales and abnormal hair.Dermatology examination showed erythroderma-like appearance in trunk and limbs,multi-ring and creeping erythema,specific"bilateral"scales,dry,slender ichthyosis-like scales;Hair abnormalities were short,brittle and dull;Eyebrows and eyelashes were sparse.Pathological examination showed:hyperkeratosis,dyskeratosis,irregular thickening of epidermis,intercellular edema,fracture,curl and loss of collagen in dermis,extravasation of red blood cells,infiltration of a small amount of inflammatory cells,and partial subcutaneous steatosis.Gene sequencing:SPINK5 gene had a homozygous missense mutation C.2423c＞T:P.T808i detected in the whole exon gene examination.According to the skin damage and genetic examination,Netherton syndrome was diagnosed.Fluticasone propionate ointment,tretinoin cream and vitamin E emulsion were given for external use in a ratio of 1∶1.This disease should be differentiated from atopic dermatitis,hyperIgE syndrome,erythroderma and omenn syndrome.