Objectives: It is still not quite clear whether mental health symptoms could be further identified correlations among the endotype, severity and health-related quality of life (HRQOL) impairment of chronic rhinosinusitis with nasal polyps (CRSwNP). Design: Prospective cross-sectional study. Setting: One tertiary care academic hospital. Methods: Patients with CRSwNP completed prospective measurements, including calculating body mass index (BMI), identifying eosinophilic CRSwNP (eCRSwNP), assessing Lund-Mackay score (LMS), 22-item Sino-Nasal Outcomes Test (SNOT-22), 14-item Perceived Stress Scale (PSS-14), as well as Hospital Anxiety and Depression Scale (HADS). Results: Of 91 patients with CRSwNP were enrolled, including 57 males (62.64%) and 34 females (37.36%), with a mean (SD) age of 46.31 (14.41) years. The scores of SNOT-22 were correlated with both the scores of anxiety ( r = 0.348; p = 0.001) and depression scale ( r = 0.217; p = 0.039). Patients younger than 60 years old (OR, 4.798; 95% CI, 1.288-17.874; p = 0.0194) and highly educated (OR, 4.726; 95% CI, 1.689-13.224; p = 0.0031) experienced more stress. Patients with marital status (OR, 0.101; 95% CI, 0.026-0.398; p = 0.0011) had less anxiety, while normal weight (OR, 0.242; 95% CI, 0.076-0.775; p = 0.016) and short history (OR, 0.216; 95% CI, 0.063-0.742; p = 0.0150) had less depression. Conclusion: Anxiety and depression symptoms were prevalent, while stress was more prevalent in CRSwNP. Anxiety and depression were correlated with HRQOL impairment. Moreover, young and highly educated patients had more stress. Marriage reduced anxiety. Patients with normal weight and short history had less depression.