Purpose: To identify the determinants of schizophrenia-specific HRQoL levels, five types of factors (i.e., sociodemographic, clinical, psychopathological, neurocognitive, and psychosocial factors) were simultaneously investigated in the same cross-sectional sample. Methods: A total of 120 patients with a diagnosis of schizophrenia but not spectrum conditions were recruited by convenience sampling. Subjective HRQoL levels were measured using the disease-specific S-QoL-C. After sociodemographic and clinical data were collected, psychopathological data were self-rated with the Beck Depression Inventory-II (BDI-II) and were assessed with the Positive and Negative Syndrome Scale (PANSS) by professionally trained raters. Two neurocognitive assessments were conducted by licensed occupational therapists (OTs). Psychosocial factors were assessed using self-reports measures, including the, General Self-Efficacy Scale (GSES), Rosenberg Self-Esteem Scale (RSES), and Social Impact Scale (SIS). All measures were administered in random order. OTs, PANSS raters, and participants were blinded to score computation, and multiple hierarchical regression with the stepwise method was conducted. Results: The S-QoL-C scores were most strongly affected by psychosocial factors and the psychopathological factors, followed by clinical and sociodemographic factors. Total scores on the BDI-II had the largest contributions to S-QoL-C index scores and seven of eight S-QoL-C subscales. In addition, the GSES, RSES, and SIS showed effects across the S-QoL-C subscales. The BDI-II, GSES, and RSES all influenced the S-QoL-C index scores, in addition to the number of hospitalizations. Conclusion: Psychosocial factors and psychopathological factors measured by the BDI-II had the greatest impact on schizophrenia-specific HRQoL levels. Psychiatric treatment programs focusing on psychosocial status and depressive symptoms can improve schizophrenia-specific HRQoL levels. (C) 2014 Elsevier B.V. All rights reserved.