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Spiritual needs are increasingly recognized as part of supportive cancer care, but they remain underassessed in routine practice. This study examined spiritual needs and associated psychosocial factors among patients with colorectal cancer recruited from 5 hospitals in Guangdong Province, China. A multicenter cross-sectional survey was conducted between July 2024 and June 2025. Patients with colorectal cancer completed validated Chinese questionnaires assessing perceived social support, psychological resilience, anxiety, depression, spiritual well-being, and spiritual needs. Data were analyzed using descriptive statistics, correlation analysis, confirmatory factor analysis, and structural equation modeling. Bias-corrected bootstrapping with 5000 resamples was used to estimate 95% confidence intervals for standardized direct, indirect, and total estimates. In total, 1068 valid questionnaires were included. Spiritual needs were negatively correlated with perceived social support, psychological resilience, and spiritual well-being and positively correlated with anxiety and depression. The structural equation model showed a good fit to the data: χ2/df = 1.434, root mean square error of approximation = 0.020, Tucker-Lewis index = 0.990, comparative fit index = 0.991, and incremental fit index = 0.991. In the hypothesized model, perceived social support, psychological resilience, and spiritual well-being were negatively associated with spiritual needs, whereas anxiety and depression were positively associated with spiritual needs. Overall, spiritual needs were associated with social support, resilience, emotional distress, and spiritual well-being. These findings support the inclusion of spiritual, psychosocial, and emotional assessment in supportive care for this population.