OBJECTIVES: In China, prenatal screening of non-invasive prenatal testing (NIPT) for Down’s syndrome is used in some hospitals with pilot purpose. There is little evidence regarding to cost-effective between NIPT and maternal serum screening(MSS). This study aimed to evaluate NIPT’s cost-effectiveness and provide evidence-based information for decision-makers in China. METHODS: The cost-effectiveness analysis of NIPT for Down’s syndrome(DS) from a societal perspective was conducted, compared with current clinical practice. Cost of NIPT, MSS, genetic counseling, diagnostic testing and  termination of pregnancy were considered. All variables were based on field surveys in four selected cities in China and a literature review in both English and Chinese database. A decision-analytic model was developed to compare 5 different strategies with 1) No screening; 2) Current clinical practice using MSS only; 3) Implementing NIPT as an optional secondary screening test for those high risk women by MSS (the contingent screening strategy); 4) NIPT for pregnancies aged over 35 years and 5) NIPT as primary screening test, replacing maternal serum screening.  RESULTS:  In current clinical practice, for a cohort of 10000 pregnant women, NIPT as primary strategy can detect 10.39 DS births which found to be the most effective. But the contingent screening strategy dominated all other screening strategies: it had the best cost effectiveness ratio ($56434.06 per case averted of DS) with fewest procedure-related miscarriages (0.02 per 10 000 pregnancies) and can detect 9.15 DS births. Sensitivity analysis shows that if the price of NIPT decreases to $44.20 (current price is $552.49), NIPT as primary strategy would be the most cost-effective.  CONCLUSIONS: Implementing NIPT as an optional secondary screening test is the preferred option for prenatal screening of women for pregnancies affected by Down’s syndrome in China.