BackgroundThe interplay between nutritional and inflammatory status and sedentary behavior is intricate, and both are associated with the prognosis of cancer survivors. However, the combined effect of these factors on the mortality rate of cancer survivors remains unclear.MethodsWe selected cancer survivors from the National Health and Nutrition Examination Survey (2007-2018). The Naples Prognostic Score (NPS) was used as an integrated marker of inflammatory and nutritional status, while sedentary behavior was quantified based on self-reported daily sitting time. Multivariable Cox proportional hazards models were employed to examine the independent and combined associations of NPS and sedentary behavior with mortality outcomes in this population.ResultsAmong 2,411 cancer survivors followed for a median of 71 months, 554 deaths occurred (cancer, 190; non-cancer, 364). High NPS correlated with higher all-cause, cancer-specific, and non-cancer mortality. Longer sedentary time was independently linked to higher all-cause and non-cancer mortality, with each additional hour of sitting per day conferring a significant rise in risk. Survivors exhibiting both high NPS and >= 6 h/day of sedentary behavior faced the greatest mortality risks: all-cause (hazard ratio [HR] 4.44, 95% CI: 2.66-7.42), cancer-specific (HR 1.92 95% CI: 1.11-3.32), and non-cancer (HR 2.81, 95% CI: 1.76-4.50).ConclusionOur findings demonstrate that nutritional and inflammatory status and sedentary behavior collectively influence mortality risk in cancer survivors. Patients exhibiting concurrent poor nutrition, systemic inflammation (high NPS), and sedentary behavior may be at higher risk of death.