<p>The effectiveness of mHealth interventions to reduce child unintentional injuries in resource-limited areas like rural areas remains poorly understood. This study aims to assess the effectiveness of a theory-driven and culturally-adapted app intervention to reduce unintentional injury incidence among rural preschoolers. A 12-month single-blinded cluster randomized controlled trial (Chinese Clinical Trial Registry, ChiCTR2000037606, registered on August 29, 2020) was conducted among 3836 preschoolers and their caregivers from 24 preschools in rural China. Participating preschools were randomly allocated using a 1:1 ratio to the intervention or control group to receive app-based education including or excluding child injury prevention. Primary outcome was the 12-month preschooler unintentional injury incidence. Secondary outcomes included caregiver’s safety-related attitudes, supervision behaviors, and home environment scores. Of the 3836 enrolled participants, 3338 (87.0%) completed the study. Results demonstrated the intervention significantly reduced preschooler unintentional injury incidence (a<i>RR</i> = 0.93, 95% CI: 0.86, 0.98) and improved caregivers’ safety-related attitudes (<i>b</i> = 0.51, 95% CI: 0.32, 0.73), supervision behaviors (<i>b</i> = 3.83, 95% CI: 3.15, 4.46), and home environment (<i>b</i> = 3.38, 95% CI: 2.51, 4.16). This trial suggests the app-based intervention effectively enhances child safety among rural preschoolers, and could be disseminated broadly in China and tailored to other resource-limited settings.</p>