Background <p>Clinical or experimental trials have shown that hydrogen-rich water has anti-inflammatory properties, but its use for keloids has not been studied. This research explores HRW’s therapeutic potential and mechanism for keloid treatment.</p> Methods <p>21 keloid patients scheduled for two-stage operations were randomly divided into the HRW treatment group (HRW group) and the control group (Con group). The HRW group received hydrogen in their drinking water, while the Con group drank hydrogen-free water. Clinical information was collected. Cytokines related to inflammation, keloid formation, and symptoms were measured using western blotting (WB), qPCR, and ELISA before and after the interventions.</p> Results <p>Patients reported a significantly lower frequency of pain and pruritus after hydrogen-rich water therapy. The VSS and pigmentation domain scores significantly decreased after hydrogen-rich water therapy. WB and qPCR results showed a significant decrease in the expression of pruritus-related cytokine TRPV1 and keloid-related cytokine HIF-1<i>α</i> after hydrogen-rich water therapy. Anti-inflammatory cytokine IL-10 levels significantly increased after hydrogen-rich water therapy, while inflammation-related cytokines VEGF and TGF-<i>β</i> levels significantly decreased.</p> Conclusions <p>Hydrogen-rich water therapy appears to be a safe and promising approach for symptom relief and inflammation modulation in keloid patients. These findings represent an exploratory, double-blinded randomized pilot trial that provides early clinical signals supporting further large-scale investigation.</p> Level of Evidence I <p>This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors &#xa0;<a href="http://www.springer.com/00266">www.springer.com/00266</a>.</p>