OBJECTIVES: Cervical Cancer (CxCa) has become a major public health issue since it has the 2^nd highest rates of incidence and mortality for Mexican women. This study aims to calculate within the Mexican public healthcare setting, the clinical and economic impact of the implementation of an hr-HPV testing with individual HPV-16/18 genotyping for CxCa primary screening and the use of p16/Ki-67 dual-stained cytology as triage compared with the current practice (cytology as primary screening and colposcopy as triage).  METHODS: Mexican epidemiology of HPV and CxCa were simulated from a public-payer perspective for two screening-cycles. Both strategies were simulated with a decision tree model. Markov methodology was performed to model natural history of CxCa.  Strategies evaluated were: 1)primary screening with hr-HPV testing with HPV-16/18 genotyping and reflex p16-Ki-67 dual-stained cytology, and 2)current practice. Cycle length was 3-yr and 1-yr length, respectively. Clinical data was taken mainly from ATHENA and PALMS trials. Direct costs were obtained from local sources. Costs for tests in strategy-1 were given by the manufacturer. All costs are in 2015 USD ($1USD=$17MXN). RESULTS: A 7.3 million cohort of women between 25-60 years-old was simulated. Percentage of ≥CIN2 detection over 2-cycles was 85.1% for strategy-1 vs 53% for strategy-2. Annual incidence of CxCa was reduced over 61.6% with strategy-1. Annual CxCa mortalities were also reduced in 60.0% with this strategy. An increased efficiency was observed with strategy-1 in colposcopies needed per ≥CIN2 case detected (3.5 vs 5.5, respectively). Total cost per screened patient/year was 54% less with strategy-1 ($8.4) vs strategy-2 ($18.4). Total costs per case ≥CIN2 detected were 8.2% lower with strategy-1 ($2,434.5 and $2,250.9, respectively). CONCLUSIONS: The incorporation of hr-HPV testing with individual HPV-16/18 genotyping as primary screening and p16/Ki-67 dual-stained cytology as triage for CxCa screening represents an efficient alternative with positive clinical and economic outcomes within the Mexican public healthcare system.