Background: To appraise comprehensively the demographic and clinical factors that may collectively contribute to demoralization, depression and negative meaning of life in patients with cancer, employing hepatocellular carcinoma (HCC) as the representative investigative subject. Purpose: To appraise comprehensively the demographic and clinical factors that collectively contribute to demoralization, depression and negative meaning of life in patients with cancer, employing hepatocellular carcinoma (HCC) as the representative malignancy for investigation in a Taiwanese population. Design: A retrospective cross-sectional study from 2019-2020 on 250 HCC patients in hospitalized and following the STROBE guidelines. Methods: Prevalence was estimated by G-power; and associations between demographic or clinical factors and scores of Mandarin versions of Demoralization Scale (DS-MV), Center for Epidemiologic Studies Depression Scale (CES-D) or Meaning in Life Scale (MiLs) were evaluated by Chi-square test or Pearson's product-moment correlation. Results: Factors with DS-MV scores higher than 30 included marital status, children as primary caregiver, gender and metastasis. Factors with CES-D scores higher than 16 included marital status, children as primary caregiver, age, monthly financial support and cancer comorbidity. Factors with MiLs scores less than 7 included marital status, and recurrence or duration of cancer. Conclusions: Marital status is a major contributing factor to all three psychological states. Children as primary caregiver impacts more critically than spouse on both demoralization and depression; gender and metastasis are akin to demoralization; age, monthly financial support and cancer comorbidity contribute to depression; and recurrence and duration of cancer impact on negative meaning of life. Impact: This is first time that collective demographic and clinical factors on the mental health of patients with liver cancer are identified. Our findings would encourage clinical nurses to be more conscious of the contribution of these factors on the emotional states of patients with cancer when performing their daily duties.