Psoriasis is a chronic dermatological disorder that has a negative impact on quality of life (QoL). This hospital-based cross-sectional study determined factors associated with health-related QoL (HRQoL) impairment in adult psoriasis patients. HRQoL was assessed using the Dermatology Life Quality Index (DLQI). Disease severity was assessed using the Psoriasis Area and Severity Index (PASI). A total of 223 patients, aged 18 to 83 years, were recruited. For 67 (30%) patients, psoriasis had very large to extremely large effect on their life (DLQI score = 11-30). The median DLQI score was 7 (interquartile range = 7). Factors significantly associated with severe impact on HRQoL (DLQI ≥ 10) were disease severity, single status, working status, sports activities, nail dystrophy, exposed area involvement, itch, disturbed sleep, stress, and infection. The factor predictive of severe impact of psoriasis on HRQoL was disease severity. A holistic approach in the management, including psychosocial issues, is absolutely crucial for the optimal care of psoriasis patients.