This paper selects six typical spaces of a university campus in Xi'an to study the comprehensive effect of heat and PM2.5 in open spaces. Subjects are required to complete a subjective perception questionnaire in a thermal-PM2.5 interactive environment combined with on-site actual measurement. The results are shown in three aspects: (1) PM2.5 has a significant effect on thermal sensation and thermal comfort in the afternoon. PM2.5 concentration of 0–20 and 20–40 μg/m³ aggravates heat sensation of the crowd in summer and reduces subjective thermal comfort. (2) At constant physiological equivalent temperature (PET), air quality comfort decreases with increase in PM2.5 concentration. Generally, PM2.5 is 20–27, 20–23, and 20–24 μg/m³ in the morning, afternoon, and evening, respectively. People are more sensitive to the air quality with the increase of PET as the quality of comfort gradually improved. (3) Further, when PM2.5 concentration decreased from 20 to 40 to 0–20 μg/m³ at night, the mean value of overall comfort vote (OCV) increased by 0.46. Therefore, this paper can provide experimental support for establishing a human thermal comfort research system under the interaction of multiple environments, and can also provide a strategic basis for improving the urban outdoor thermal environment and air quality.