Most studies on the health effects of PM2.5 (fine particulate matter with diameter smaller than 2.5 μm) use indirect indicators, such as mortality and number of hospital visits. Recent research shows that biomarkers can also be used to evaluate the health effects of PM2.5; however, these biomarkers are not very common. Clinical laboratories can provide a significant amount of test data that have been proven to have important diagnostic value. Therefore, we use big data analysis methods to find the associations between clinical laboratory common test items and PM2.5 exposure. Data related to air pollution and meteorological information between 2014 and 2016 were obtained from the China National Environmental Monitoring Centre and the China National Meteorological Information Center. Additionally, data of 27 common test items from the same period were collected from Changsha Central Hospital. Primary analyses included a generalized additive model to analyze the associations between PM2.5 concentration and common test items; the model was adjusted for time trends, weather conditions (temperature and humidity), and days of the week. Furthermore, we adjusted the effects of other air pollutants, such as PM10, SO2, NO2, CO, and O3. 17 items such as TP, ALB, ALT, AST, TBIL, DBIL, UREA, CREA, UA, GLU, LDL, WBC, K, Cl, Ca, TT, and FIB were significantly positively associated with PM2.5 concentration (P< 0.05) and have concentration-response relationship. After adjusting the effect of PM10+SO2+NO2+CO+O3, TP, ALB, ALT, AST, TBIL, DBIL, UREA, CREA, UA, GLU, WBC, Cl, and Ca were still significantly associated with PM2.5 concentration (P< 0.05). This current study suggested that clinical laboratory common test items may be used to assess and predict the health effects of PM2.5 on the population.