OBJECTIVE: This study aimed to investigate the correlation of serum calprotectin expression with risk and severity of psoriasis, as well as its predictive value for clinical response to tumor necrosis factor inhibitors (TNFi) treatment in psoriasis patients. PATIENTS AND METHODS: 72 psoriasis patients and 70 health controls (HCs) were enrolled. Blood samples were collected, and serum calprotectin was determined by commercial enzyme-linked immuno sorbent assay (ELISA). All patients were treated by TNFi treatment, and followed up at 6 months, and the last follow-up date was 2016/11. RESULTS: Calprotectin level was elevated in psoriasis patients compared to HCs (p < 0.001), and it disclosed a good diagnostic value of psoriasis with area under curve (AUC) 0.872, 95% CI: 0.810-0.935. Calprotectin expression was positively associated with Psoriasis Area and Severity Index (PASI) score (R = 0.452, p < 0.001), while it was not associated with BSA (R = 0.125. p = 0.297). 58.3% patients achieved PASI75 and 43.1% patients achieved PASI90 at M6. Calprotectin was decreased during the 6-month treatment (p < 0.001). Changes of calprotectin during the first month (Delta calprotectin (M0-M1)) in PASI75 group were more than that of non-PASI75 group (p < 0.001). Also, multivariate logistic analysis revealed that Delta calprotectin (M0-M1) (p = 0.001) was an independent factor for PASI75 achievement at M6 after TNFi treatment, while pre-systemic biologic treatment (p = 0.001) was an independent factor for non-PASI75 achievement. CONCLUSIONS: Serum calprotectin expression is correlated with risk and severity of psoriasis, and the decrease of calprotectin during the first month could predict better clinical response to TNFi treatment in psoriasis patients.