A 49-year-old male patient who had been diagnosed with variable hairy cell leukemia (HCL-V) was treated with interferon for half a year but exert no obvious effect. After two courses of chemotherapy with cladribine, he achieved remission, and splenomegaly significantly improved (the length in craniocaudal dimension decreased from 15.8cm to 11.8cm). Four years later, the patient got disease relapse and was recommended for another cycle of cladribine (6mg for 7 days). On the last day of cladribine, the patient developed fever with needle-like red rashes on the face, limbs, and trunk. At the very beginning, the rash was lighter in color, sparsely distributed, and without obvious itching. Three days later, the rash gradually darkened, expanded and merged, with itching. With the application of high dose gamma globulin and corticosteroids (prednisolone combined with dexamethasone), the rash finally faded, and the patient was discharged. Rash caused by cladribine is not uncommon, such serious and widespread drug-induced rash is rare, and there are few reports. This article reviewed relevant studies and treatments.