Background Mental health problems are important public health issues among college students and are associated with various social factors. However, these influencing factors were scarcely summarized in Chinese college students comprehensively. This study aims to assess the associations between socio-demographic characteristics, lifestyles, social support quality (SSQ) and mental health among Chinese college students . Methods A cross-sectional study was conducted in Wuhan, China, from October 2017 to February 2018. College students from 18 colleges or universities were randomly recruited using multi-stage cluster sampling method. The Multidimensional Scale of Perceived Social Support scale and 12-items General Health Questionnaire were used to estimate students' SSQ and mental health statuses, respectively. Logistic regression analysis was used to evaluate the associations between socio-demographic characteristics, lifestyles, SSQ and mental health problems. Results A total of 10,676 college students were included. Among them, 21.4% were identified as having possible mental health problems. Students being a female, aged 18-22 years old, whose mother held college degrees and above, and drinking alcohol were more likely to have mental health problems (P < 0.05). Contrarily, having general or higher household economic levels, work-rest regularly, and sleeping >= 7 h were preventive factors (P < 0.05). Especially, a decreasing trend in the risk of having mental health problems with the improvement of SSQ was identified. Conclusion Besides socio-demographic and lifestyle factors, social support is a critical factor for mental health among college students. Improving SSQ, especially which from the family, could be an effective method to prevent mental health problems among college students.