Objectives: Under current global climate conditions, there are insufficient studies on the health influences of cold spells, especially on mental health. This study aimed to examine the effect of cold spells on schizophrenia admissions and to analyze the potential interaction effect with the air quality index (AQI). Methods: Daily data on schizophrenia admissions and climatic variables in Hefei were collected from 2013 to 2019. Based on 20 definitions, the impacts of cold spells were quantified separately to find the most appropriate definition for the region, and meta-regression was used to explore the different effect sizes of the different days in a cold spell event. In addition, the potential interaction effect was tested by introducing a categorical variable, CSH, reflecting the cold spell and AQI level. Results: The cold spell defined by temperature below the 6th centile while lasting for at least three days produced the optimum model fit performance. In general, the risk of schizophrenia admissions increased on cold spell days. The largest single-day effect occurred on the 12th day with RR = 1.081 (95% CI: 1.044, 1.118). In a single cold spell event, the effect of the 3rd and subsequent days of a cold spell (RR = 1.082, 95% CI: 1.036, 1.130) was higher than that on the 2nd day (RR = 1.054, 95% CI: 1.024, 1.085). Similarly, the effect of the 2nd day was also higher than that of the 1st day (RR = 1.027, 95% CI: 1.012, 1.042). We found a synergistic effect between cold spells and high AQI in the male group, and the relative excess risk due to interaction (RERI) was 0.018 (95% CI: 0.005–0.030). Conclusions: This study suggested that the impacts of cold spells should be considered based on the definition of the most appropriate for the region when formulating targeted measures of schizophrenia. The discovery of the synergistic effect was referred to help the selection of the timing of precautions for susceptible people.