A nationwide survey was conducted from October 2018 to September 2019 to assess the prevalence of hyperhomocysteinemia (Hhcy) and its influencing factors in China. A standardized questionnaire was used to collect information. Hhcy was defined as the level of serum homocysteine (HCY) \ge15.0 µmol/L. The H-type hypertension (HHYP) was defined as hypertension with an elevated serum HCY (\ge15.0 µmol/L). Finally, 110 551 residents \ge40 years of age from 31 provinces in the mainland of China were included. Overall, the median serum HCY level was 10.9 µmol/L (interquartile range 7.9–15.1). A total of 28 633 participants (25.9%) were defined as Hhcy. The Hhcy prevalence ranged from 7.9% in Shanghai to 56.8% in Tianjin. The data showed that serum HCY levels were associated with age, male gender, cigarette smoking, hypertension, diabetes, ethnicity, endurance in exercise (inverse), and fruit and vegetable intake (inverse). In addition, 15 486 participants were defined as HHYP, and the rate was 14.0%. HHYP was an independent predictor of stroke with an adjusted odds ratio of 1.752 (95% CI 1.338–2.105). The geographical distribution pattern of the Hhcy epidemic reflects dynamic differences, and national strategies should be carried out to further improve the care of patients with Hhcy across China.