BACKGROUND: The infection of human immunodeficiency virus (HIV) is 1 of the major causes of morbidity and mortality in the world. People with chronic diseases have a higher risk of depression. The HIV people are more likely to suffer from depression. Appropriate psychosocial interventions are effective, but their accessibility is limited by the resources needed for their transmission. Thus, it makes sense to develop more cost-effective alternatives, for instance the web-based intervention (WBI), which may be effective for the well-being and depression. The aim of our program is to explore the effects of a WBI on depressive symptoms and well-being in HIV-infected patients. METHOD: It is a randomized controlled experiment to be conducted from February 2021 to July 2021. It was permitted through the Ethics Committee of Changshan County People's Hospital (no.60928376). This study includes 100 HIV patients. Inclusion criteria: (1)18 + years, on effective antiretroviral therapy≥ 1 year before inclusion. Exclusion criteria: patients with severe kidney, liver, lung, and heart diseases. Patients are divided randomly into the study group and control group, each group is assigned 50. The primary results are subjective well-being and depressive symptoms, while the secondary result involves the patients' satisfaction with life. RESULTS: The following Table 1 will exhibit the comparison of outcomes between 2 groups. CONCLUSION: HIV infected patients can benefit from WBI, which can be utilized as an adjunct to medical treatment. TRIAL REGISTRATION NUMBER: researchregistry6215.