BackgroundDespite the high cure rate of differentiated thyroid cancer (DTC), patients endure side effects from treatment and psychological distress, impacting their quality of life. The potential of mobile health (mHealth) interventions to address these issues remains unexplored. The purpose of this study is to develop an mHealth intervention based on the Multi-Theoretical Model of Health Behavior Change (MTM) and evaluate its impact on reducing anxiety, depression, fear of cancer progression, and enhancing quality of life in DTC patients.MethodsA single-blind, single-center, prospective, randomized controlled trial was conducted. One hundred and eleven consecutive DTC patients from Harbin Medical University’s Fourth Hospital were enrolled from March 2023 to March 2024. Participants were randomized into a control group and an intervention group that received a 3-month mHealth intervention based on MTM theory. Outcomes were assessed using web-based questionnaires at baseline and conclusion.ResultsOne hundred four patients with DTC completed the study, with 7 lost to follow-up (6.3%). The intervention group experienced a significant drop in PHQ-4 scores post-MTM-mHealth intervention (P < .026), with no change in the control group, demonstrating a significant difference. The intervention group also had significantly lower anxiety (P < .015) and depression (P < .032) scores compared to controls. All PHQ-4 scores improved in the intervention group except for “Little interest or pleasure in doing things.” Anxiety levels were significantly lower in the intervention group (P < .026) but remained unchanged in controls. The control group exhibited a significant increase in FCR-4 scores at follow-up, differing from the intervention group (P < 0.001). Quality of life scores did not differ at baseline but saw a significant improvement in the intervention group, while the control group experienced no significant change. The intervention group had higher VAS scores (P < .030) and greater health education satisfaction across all dimensions (P < .019).ConclusionsThe MTM-based mHealth intervention significantly benefits DTC patients by reducing anxiety, fear of cancer recurrence, and improving quality of life, though its effect on depression requires further investigation.Trial registrationChina Clinical Trial Registry ChiCTR2200064321.