Hyaluronic acid (HA) is among the most effective and safe ingredients frequently used in cosmetics. However, a more economical and efficient formulation is still required. We sought to assess the safety and efficacy of a novel hydrogel manufactured only by irradiation containing cross-linked HA and polyethylene glycol polymers with addition of polysiloxane. The study included 30 people with normal skin and 30 patients with xerosis. In the normal skin group, to evaluate the safety, a patch test and a photopatch test were performed, and patients' discomfort was investigated. In those with xerosis, to assess the efficacy, a skin barrier function test was performed at baseline and at 2, 4, and 8 weeks after the application of the novel hydrogel. Additionally, the xerosis severity scale (XSS), patient satisfaction, Investigator's Global Assessment (IGA), and adverse responses were evaluated. In the safety study, there was no significant discomfort in the experimental group compared with the control group. In the efficacy study, at 2, 4, and 8 weeks after the application of the novel hydrogel, the mean value of skin hydration and sebum content increased and the mean value of XSS decreased with time in the experimental group, and a difference was observed when compared with the control group. IGA showed improvement in 97%, 77%, and 80% at each visit and the proportions of satisfied patients were 90%, 87%, and 90%, respectively. The novel HA-based hydrogel tested herein could be a safe and effective therapeutic remedy for xerosis.