Background: During the past decade an increasing number of people live with advanced cancer mainly due to improved medical treatment. Research has shown that many people with advanced cancer have problems with everyday activities, which have negative impact on their quality of life, and that they spend a considerable part of their time at home. Still, research on interventions to support the performance of and participation in everyday activities is only scarcely available. Therefore, the occupational therapy-based "Cancer Home-Life Intervention" consisting of tailored adaptive interventions applied in the participant's home environment was developed. The objective of this study is to examine the effectiveness and cost-effectiveness of the Cancer Home-Life Intervention compared to usual care on the performance of and participation in everyday activities and quality of life in people with advanced cancer living at home. Methods: The study is a randomised, controlled trial (RCT) including an economic evaluation. The required sample size of 272 adults living at home will be recruited from outpatient clinics at two Danish hospitals. They should be diagnosed with cancer; evaluated incurable by the responsible oncologist; and with a functional level 1-2 on the WHO performance scale. The primary outcome is the quality of performance of activities of daily living. Secondary outcomes are problems with prioritised everyday activities; autonomy and participation; and health-related quality of life. Participants are randomly assigned to: a) The Cancer Home-Life Intervention in addition to usual care, and b) Usual care alone. Discussion: The trial will show whether the Cancer Home-Life Intervention provides better support for people with advanced cancer living at home in performing and participating in everyday activities, and whether it contributes to their health-related quality of life. The economic evaluation alongside the RCT will show if the Cancer Home-Life Intervention is cost-effective. The trial will also show the acceptability of the intervention to the target group, and whether subgroups of participants will benefit more than others. Trial registration: ClinicalTrials.gov Identifier NCT02356627. Registered 02/02/2015.