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Chronic illness is associated with lower quality of life, yet it remains unclear whether this association differs by employment arrangements, particularly gig work. Using longitudinal data (2019-2024) from a nationally representative sample of 22,712 British workers, we examined how regular and gig employment moderate the association between chronic illness and psychological distress (GHQ-12; range: 0-12). Random-effects models indicate that individuals with chronic illness report 1.44 points higher psychological distress than those without such conditions (p < 0.001). This association is weaker among individuals in regular employment and low-dependence gig work, who report 0.64 and 0.56 points lower psychological distress, respectively, than those who are unemployed (p < 0.001). Although women with chronic illness experience greater psychological distress overall, among men with chronic illness, high-dependence gig work is associated with a 1.60-point increase in psychological distress relative to regular employment (p = 0.004), whereas no such pattern is observed among women. Taken together, the moderating role of gig work in health-related quality of life varies with workers' dependence on gig work. Reducing the mental health burden of chronic illness may require access not only to employment, but also to high-quality jobs.