Abstract：Objective To explore the reform of the operating mechanism of centers for disease control and prevention ( CDCs ) in the new era, and to put forward recommendations. Methods We collected the financial investment and staffing of CDCs in Zhejiang Province from 2018 to 2020 through China Disease Prevention and Control Information System and Zhejiang Health Statistical Yearbook. We conducted a questionnaire survey among 620 staffs selected by convenience sampling, and a qualitative interview among 40 leaders and experts from CDCs and general hospitals in Zhejiang Province. Results By the year 2020, there were 105 CDCs in Zhejiang Province, including 1 province-level, 11 prefecture-level, 90 county-level and 3 development zone-level ones. The revenues were mainly from financial subsidy and business incomes, which were over expenditures. There were 7 008 posts in CDCs, with a staffing allocation ratio of 1.29/10 000. Among the reform measures of operation mechanism of CDCs, the flexible communication between clinicians and public health doctors was highly approved (90.03%); among the reform measures of enhancing the integration of prevention and treatment, further clarifying the public health functions of hospitals and ensuring financial compensation was highly approved (74.01%). Conclusion We should further stimulate the endogenous power and vitality of CDCs, strengthen the construction of talent team, promote the active integration of hospitals and CDCs, and improve public health level.