Background: Phthalates can cause respiratory and immunological disorders. However, little is known about the role of serum periostin and YKL-40 levels in mediating the effects of phthalates. We investigated the mediating role of these biomarkers in the relationship between phthalates and airway dysfunction. Methods: A total of 487 children (aged 10 to 12 years-old) were examined. Four high-molecular-weight phthalate (HMWP) [Σ4HMWP] metabolites and 3 low-molecular-weight phthalate (LMWP) [Σ3LMWP] metabolites in urine samples were measured. Serum periostin and YKL-40 levels were measured. Airway function was measured using impulse oscillometry. A mediation model was used to quantify the mediating effects of periostin and YKL-40 on airway dysfunction. Results: After adjustment for height, gender, BMI z-score, aeroallergen sensitization, secondary smoking, and vitamin D level, the level of urinary Σ3LMWP metabolites was significantly associated with respiratory system resistance at 5 Hz (Rrs5; adjusted β: 0.020, 95% CI: 0.005 to 0.034; P = .010). The levels of urinary Σ4HMWP and Σ3LMWP metabolites were significantly associated with periostin level, but not with YKL-40 level. In addition, the periostin level was associated with Rrs5 (adjusted β: 0.048, 95% CI: 0.015 to 0.081; P = .005) and Rrs20-5 (adjusted β: 0.040, 95% CI: 0.011 to 0.069; P =.007). Serum periostin level had a significant effect in mediating the relationship between Σ3LMWP and Rrs5 (13.9%, 95% CI: 10.7 to 77.0; P < .001). Conclusion: Exposure to LMWPs was significantly associated with airway dysfunction, and this effect was partially attributable to increased serum periostin level.