To evaluate the cost-effectiveness of ribociclib plus fulvestrant versus fulvestrant in hormone receptor-positive/human EGF receptor 2-negative advanced breast cancer. A three-state Markov model was developed to evaluate the costs and effectiveness over 10 years. Direct costs and utility values were obtained from previously published studies. We calculated incremental cost-effectiveness ratio to evaluate the cost-effectiveness at a willingness-to-pay threshold of $150,000 per additional quality-adjusted life year. The incremental cost-effectiveness ratio was $1,073,526 per quality-adjusted life year of ribociclib plus fulvestrant versus fulvestrant. Ribociclib plus fulvestrant is not cost-effective versus fulvestrant in the treatment of advanced hormone receptor-positive/human EGF receptor 2-negative breast cancer. When ribociclib is at 10% of the full price, ribociclib plus fulvestrant could be cost-effective.