Background: Self-medication has become a common phenomenon. Economic factors are important factors that affect the self-medication of residents. This study aimed to investigate the current status of self-medication behaviors in China and explored the related factors affecting considerations associated with medical insurance reimbursement or drug price in self-medication. Methods: A national cross-sectional investigation was conducted among Chinese people over 18 years old under a multi-stage sampling method through a questionnaire, which includes demographic sociological characteristics, self-medication behaviors and scales. The Chi-square test was used to analyze whether the respondents consider medical insurance reimbursement or drug price as an important factor when purchasing over-the-counter (OTC) drugs. Logistic regression was used to examine the associated factors of considering medical insurance reimbursement or drug price. Results: In total, 9256 respondents were included in this study; 37.52% of the respondents regarded drug prices as an important consideration, and 28.53% of the respondents attached great importance to medical insurance reimbursement. Elderly respondents who lived in the central region, had medical insurance, and had lower levels of health literacy were more likely to consider the medical insurance reimbursement, while respondents with high monthly family income as well as students were less likely to consider the same issue (p < 0.05). Respondents settled in the central and western regions, students, those without fixed occupations, those who suffered from chronic diseases, or those with lower health literacy were more likely to consider drug prices, while the respondents with bachelor degrees, urban population and high per capita monthly income were less likely to consider the drug prices (p < 0.05). Conclusion: Self-medication behaviors with OTC drugs were prevalent in China, and consideration factors of medical insurance reimbursement or drug prices were related to socio-demographic characteristics and health literacy. There is a need to take measures to reduce the economic burden of self-medication, improve the health literacy of residents and strengthen public health education.