<p>Influenza remains a major global public health concern, and growing evidence suggests that air pollution may influence its incidence. However, most existing studies have relied on syndromic surveillance data, limiting the validity of their findings. This study investigates the association between short-term exposure to six ambient air pollutants (PM_2.5, PM₁₀, SO₂, NO₂, O₃, and CO) and laboratory-confirmed influenza cases in Shanghai from 2013 to 2017. Using a time-stratified case-crossover design and individual-level exposure estimates derived via inverse distance weighting, we evaluated multiple lag structures to characterize exposure-response relationships. Results indicated that elevated concentrations of PM_2.5, PM₁₀, SO₂, NO₂, and CO were significantly associated with increased influenza risk, while higher O₃ levels were linked to a reduced risk. Specifically, a 10&#xa0;µg/m³ increase in PM₁₀ concentration was associated with an elevated influenza risk (OR = 1.019, 95% CI: 1.004–1.034), whereas a corresponding increase in O₃ concentration was associated with a 4.1% reduction in risk (OR = 0.959, 95% CI: 0.941–0.977). Positive associations for the other pollutants were consistently observed across multiple single-day and moving average lag periods. Effect estimates exhibited marked heterogeneity by demographic characteristics, season, and city, with notable differences observed between Shanghai, Beijing, and Shenzhen. Our findings highlight the importance of considering lag effects, nonlinear exposure patterns, and regional variability in assessing the health impacts of air pollution. This study offers robust evidence to support targeted air quality management and influenza prevention strategies.</p> Graphical Abstract <p></p>