Objective <p>To clarify the association between daily sitting time and accelerated aging in women, and explored that systemic immune-inflammation index and creatinine together play an important mediating effect throughout the process.</p> Methods <p>A total of 5578 women during 2007 to 2010 from the National Health and Nutrition Examination Survey was utilized in this study. Phenotypic age calculation, logistic regression analysis, restricted cubic spline model, and subgroup analysis were employed to investigate the association between daily sitting time and accelerated aging as well as its influencing factors.</p> Results <p>The threshold effect analysis identified 7&#xa0;h as the inflection point. For every hour of sitting above the inflection point, the risk of accelerated aging will increase by 12.00%. Logistic regression analysis indicated that, compared to women who spent less than 4&#xa0;h being sedentary during the day, the risk of accelerated aging increased 49.0%, 77%, 110% in the women spent 4 ~ 6&#xa0;h (OR = 1.49, 95%CI 1.18,1.88, <i>p</i> = 0.0008), 6 ~ 8&#xa0;h(OR = 1.77, 95%CI 1.36, 2.28, <i>p</i> &lt; 0.001) and at least 8&#xa0;h(OR = 2.10, 95%CI 1.70, 2.61, <i>p</i> &lt; 0.001) respectively. Restricted cubic spline models validated nonlinear associations between the systemic immune-inflammation index, creatinine, and accelerated aging (p for nonlinearity &lt; 0.001). Parallel mediation analysis found that although systemic immune-inflammation index and creatinine had significant mediating effects (<i>p</i> &lt; 0.001) in the process of daily sitting time leading to accelerated aging, and they were a parallel double mediation effect.</p> Conclusions <p>Prolonged sitting time is significantly associated with accelerated aging, systemic immune-inflammation index and creatinine levels play important mediating roles in this process.</p>