INTRODUCTION: Understanding the biological mechanism of subjective cognitive decline (SCD) in preclinical Alzheimer's disease (AD) and identifying those who will soon convert to mild cognitive impairment (MCI) are critical for developing appropriate strategies for early diagnosis and intervention of AD. We present the study protocol of the Sino Longitudinal Study on Cognitive Decline (SILCODE), a longitudinal observational study focusing on SCD in the context of AD. METHODS AND ANALYSIS: Within SILCODE, approximately 800 subjects with SCD who are between 50 and 79 years old will be recruited through standardised public advertisements or memory clinics. They will undergo extensive assessment, including clinical and neuropsychological assessments, blood sample collection for plasma beta-amyloid and ApoE genotype, urine samples collection for AD7c-NTP, and multimodal MRI scans (structural MRI, diffusion tensor imaging, resting-state functional MRI and optional task-based functional MRI) as well as optional glucose metabolism and amyloid positron emission tomography. Subjects will be contacted by telephone every 3 months and interviewed, on average, every 15 months for 5 years. The study endpoint is the development of mild cognitive impairment or dementia. Jak & Bondi's actuarial neuropsychological method will be used for diagnosis of MCI. The least absolute shrinkage and selection operator logistic regression model followed by the sub-distribution hazard function model with death as a competing risk will be constructed to establish risk prediction models. ETHICS AND DISSEMINATION: The ethics committee of the Xuanwu Hospital of Capital Medical University has approved this study protocol (ID: [2017]046). The results will be published in peer-reviewed journals and presented at national and international scientific conferences. TRIAL REGISTRATION NUMBER: NCT03370744; Pre-results. © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.