In a prospective uncontrolled observational study we investigated the influence of gender, resilience, and marital satisfaction on mental distress of patients suffering from lung cancer and their partners. Female patients and partners reported impaired physical and mental health as well as lower resilience and marital satisfaction than males. Mental distress was negatively associated with resilience and marital satisfaction, both, in patients and their partners. We found a partial mediation effect of resilience and marital satisfaction on the relationship between gender and mental distress. Taking these results into account, particularly female patients and partners should preferably receive psychooncological support.