Hand eczema is a common, multifactorial, dermatologic condition. The prognosis is thought to be poor regard to the high possibility to become chronic and relapsing. Topical potent corticosteroid is the mainstay for treatment, but it may cause numerous adverse effects. Timolol, a non-selective beta-adrenergic antagonist, is shown to have the ability to repair the barrier function of the skin. Therefore, this study aims to evaluate the efficacy of topical timolol 0.5% versus desoximetasone 0.25% in the treatment of chronic hand eczema. A total of six volunteers who has bilateral chronic hand eczema is mild to moderate Physician Global Assessment (PGA) severity were collected to participate clinical prospective, randomized, double-blinded, intraindividual, right-left comparative trial for 8 weeks. Topical treatments, timolol 0.5% and desoximetasone 0.25% were randomly assigned to be applied on either left or right hand. The results were interpreted by Hand Eczema Severity Index (HECSI) and digital photograph. After eight weeks of intervention, both timolol and desoximetasone treated sides showed a comparable downtrend in HECSI. No serious adverse effects developed in both interventions. In conclusion, timolol 0.5% showed a promising result for chronic hand eczema treatment. Larger studies are needed to confirm its efficacy.