Background: Despite tremendous investment worldwide, hypertension treatment and control rates remain low, suggesting that contemporary population-based hypertension management may have reached its efficacy ceiling. The complexity and long-term dynamics of influencing factors make personalized management inevitable and challenging. This protocol describes Personalized Hypertension Management in Anhui, China (PHMA), a project that uses a package of innovative approaches in tailoring interventions to individual patient’s dynamic complications and contexts.Methods/design: PHMA strives to reduce hypertension harms by eight proven “objective behaviors” (e.g., self-monitoring and reporting, healthy diet, physical exercise/activities). These objective behaviors are promoted through five intervention measures: support for self- monitoring, supervised machine communications, daily education or reminder messages, weekly blood pressure notification, and quarterly signed feedback. PHMA uses ten categories and over 300 variables in selecting and refining intervention procedures and content for individual patients. Efficacy of the intervention package is evaluated using a cluster randomized controlled trial design involving a total of 60 site communities and 3352 hypertension patients. Primary measure for the evaluation is systolic and diastolic blood pressure; while secondary evaluation measures include quality of life (EQ5D-5L), occurrence of hypertension-related complications (such as cerebral hemorrhage, coronary heart disease, myocardial or cerebral infarction), healthcare utilization and scores of objective behaviors.Discussion: PHMA uses novel, low cost and sustainable approaches to tailor interventions to the dynamic conditions and contexts of individual patients. Unlike contemporary approaches to hypertension management which are mainly population based, each participant patient in PHMA applies a unique intervention package and all messages, feedbacks and other materials sent out to individual patients are different from each other. PHMA is the first project that adopts so comprehensive tailoring and if proved effective, it should have important implications for future research, practice and policy-making.Trial registration: Registered July 17, 2020. ISRCTN10999269.