BACKGROUND:It is unclear whether and how the prevalence of systemic comorbidities in oral cancer patients would change with socioeconomic development. MATERIALS AND METHODS:A retrospective study of association between socioeconomy and prevalence of systemic comorbidities in oral cancer patients from 2003 to 2017 was performed in Guangxi Province, a southwestern part of China. According to the Union for International Cancer Control (UICC) classification, 2814 patients with squamous cell carcinoma (SCC) of the lip, oral cavity, and oropharynx and 423 patients with ameloblastoma were collected and assigned to the oral cancer group and control group, respectively. Then, comparisons between the socioeconomy and healthcare expenditure in Guangxi Province, the whole China, and the USA were carried out. RESULTS:The prevalence of systemic comorbidities in oral cancer patients increased from 0.820% in 2003 to 32.302% in 2017, which was significantly higher than that in non-cancer patients(P < 0.001) and was positively correlated with the increase in gross regional product (GRP) (r = 0.911, P < 0.001) and per capita GRP (r = 0.910, P < 0.001) of Guangxi Province. In addition, the prevalence of cardiovascular diseases has the largest correlation coefficient with GRP(r = 0.957, P < 0.001) and per capita GRP(r = 0.959, P < 0.001). And the prevalence of endocrine diseases increased by 13.402% and exhibited the most significant increase in 15 years. The per capita health care expenditure of Guangxi Province and whole China was nearly equal (P = 0.353). Although the health care expenditure of Guangxi Province had been increasing year by year, its proportion in GRP remains far below that of the USA. CONCLUSIONS:With socioeconomic growth, oral cancer patients in Guangxi Province are more common to comorbid with systemic diseases. Cardiovascular and endocrine diseases may be the most susceptible systemic comorbidities in oral cancer patients to the socioeconomic status. In order to control the prevalence of systemic diseases, the government of Guangxi Province may need to expend more budgets in the health care. CLINICAL RELEVANCE:Clinicians need to pay more attention to the detection of systemic comorbidities and the concept of multidisciplinary collaboration. Instructing oral cancer patients to treat and control systemic comorbidities is also an indispensable part in the treatment of oral cancer.