Background People living at home with advanced illness require around-the-clock care. Telephone-based advice lines are critical for accessing help, yet evidence is limited. Aim To explore out-of-hours telephone-based advice lines available to adults living at home with advanced illness and their carers across the UK, and construct a practical framework to improve services. Design Structured qualitative interviews with thematic analysis. A patient and public involvement workshop was conducted to refine the proposed framework. Setting/participants Professionals with palliative/end-of-life care commissioning responsibilities, or knowledge of out-of-hours service provision, were purposively sampled to ensure UK-wide representation. Results Seventy-one interviews were conducted, covering 60 geographical areas. Five themes were identified. Availability: Ten models of advice lines were described. Variation led to confusion about who to call and when. Accessibility, awareness and promotion: It was assumed that patients/carers know who to call out-of-hours, but often they did not. Practicalities: Call handlers skills/expertise varied, which influenced how calls were managed. Possible responses ranged from simply signposting to organising home visits. Integration/continuity of care: Integration between care providers was limited by electronic medical records access and information sharing. Service structure/commissioning: Sustained funding was often an issue for charitably funded organisations. Conclusions Multiple advice lines lead to confusion and delays in obtaining care, as many default to general out-of-hours advice lines. Dedicated advice lines are valuable for patients with advanced illness as long as they are implemented well. A practical framework (including a comprehensive overview of components) is provided for guiding how these are delivered.