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Background: The role of palliative care for end-stage renal disease (ESRD) patients have been proven in some developed countries, but it is still unclear in the mainland of China. In fact, patients with ESRD experience many unmet palliative care needs, such as physical, psychological, social and spiritual needs, but the factors influencing these needs have not investigated. Methods: A cross-sectional study was conducted at two hemodialysis centers in the mainland of China from January to September 2022. Convenience sampling was used to collect data on the participants' socio-demographics, clinical characteristics, the Palliative Care Outcome Scale (POS), the Dialysis Symptom Index (DSI), the Karnofsky Performance Status Scale (KPS), the Patient Health Questionnaire-9 item (PHQ-9), and the Social Support Rate Scale (SSRS). Data were analyzed using latent profile analysis, Kruskal–Wallis test, one-way analysis of variance (ANOVA), the chi-square test and multinomial logistic regression analysis. Results: Three hundred five participants were included in this study, and divided palliative care needs into three categories: Class 1, mild palliative care needs (n = 154, 50.5%); Class 2, moderate palliative care needs (n = 89, 29.2%); Class 3, severe palliative care needs (n = 62, 20.3%). Based on the analysis of three profiles, the influencing factors of unmet needs were further analyzed. Compared with Class 3, senior high school education, the household per capita monthly income < 2,000, low KPS scores, high PHQ-9 scores, and low SSRS scores were less likely to be in Class 1 (OR = 0.03, P = 0.012; OR = 0.003, P < 0.001; OR = 1.15, P < 0.001; OR = 0.55, P < 0.001; OR = 1.35, P = 0.002; respectively) and Class 2 (OR = 0.03, P = 0.007; OR = 0.05, P = 0.011; OR = 1.10, P = 0.001; OR = 0.60, P = 0.001; OR = 1.32, P = 0.003; respectively), and high symptom severity were less likely to be in Class 1 (OR = 0.82, P = 0.001). Moreover, compared with Class 1, the household per capita monthly income < 2,000 (OR = 16.41, P < 0.001), high symptom severity scores (OR = 1.12, P = 0.002) and low KPS scores (OR = 0.95, P = 0.002) were more likely to be in Class 2. Conclusions: This study showed that almost half of ESRD patients receiving MHD presented moderate to severe palliative care needs, and the unmet needs were mainly affected by education level, financial pressure, functional status, symptom burden and social support. In the future, it is important to identify the populations with the greatest need for palliative care and consider the influencing factors of unmet needs from a comprehensive perspective, so as to help them improve health-related quality of life. [ABSTRACT FROM AUTHOR]