Children with a chronic disease, such as cystic fibrosis or juvenile arthritis, often face obstacles that can have a negative impact on children's physical, social-emotional and cognitive development, beyond the actual illness itself. Children with chronic conditions are, on average, lonelier than their peers without such conditions. Feelings of loneliness in children and adolescents have been associated with a wide range of negative outcomes, including school drop-out, depressive symptoms, social anxiety, suicide ideation, low self-esteem, eating disorders, and sleep problems. As such, the present investigation sets out to reduce these feelings of loneliness for children with chronic conditions, and aims to do so by the structured design of an applied gaming intervention. Specifically, the present paper contributes (1) a literature-based understanding on training socioemotional skills as a novel means to reduce feelings of loneliness in chronically ill children, (2) intervention objectives that are aligned to this goal, and (3) a structured proposal for design guidelines that implement the intervention objectives into 'Ruby's Mission'; an applied gaming intervention for reducing loneliness of children with chronic illness.