Objective: The purpose of this study was to compare the characteristics and related factors upon quality of life (QOL) in undergraduates between Macao and Guangzhou, and presented the correspondent advice. Methods. A self-designed questionnaire scored 1 to 5 points was completed by 818 Macao and 1580 Guangzhou undergraduates were to assess QOL in the last two weeks. Results: Compared with Guangzhou Undergraduates, lower scores were found in social and environmental domains, and self-assessed total scores while higher scores were found in independent domain in Macao students. The facets of one independent, two physical and six environmental domains were the main influencing factors to affect QOL in Macao students. As well as gender and grade for Guangzhou undergraduates, QOL was also affected by one items for physical, two for social and environmental, and three for psychological domains. Conclusion: Undergraduates in Macao or Guangzhou had their own characteristics upon QOL. Different ways should be adopted to improve QOL for local undergraduates corresponding to their influencing factors.