Purpose <p>To identify the dynamic change and explore the longitudinal correlates of demoralization in patients after cancer diagnosis, provide comprehensive references for interventions targeting demoralization at different time points.</p> Methods <p>This study included 127 cancer patients from a tertiary hospital in Guangzhou, China. Demoralization was assessed at three time points: 1 (T1), 3 (T2), and 6 (T3) months after cancer diagnosis. The study employed a cross-lagged panel network analysis to explore the longitudinal interactions in demoralization.</p> Results <p>There were 52%, 55.4%, and 56.0% of the participants reported high demoralization in 1, 3, and 6&#xa0;months after cancer diagnosis, respectively. In T1–T2, the strongest direct influence was D1 (“There is a lot of value in what I can offer others”)-D21 (“I feel sad and miserable”) (<i>B</i> = 0.32), D24 (“I feel trapped by what is happening to me”) was the most influential in-prediction and out-prediction variable in this cross-lagged network. In T2–T3, the strongest direct influence was D9 (“I feel hopeless”)-D13 (“I have a lot of regret about my life”) (<i>B</i> = 0.24), and the D9 was the most influential out-prediction variable in the cross-lagged network.</p> Conclusion <p>Considering feeling trapped and hopelessness reported the highest prediction of other symptoms in T1–T2 and T2–T3, respectively, clinical interventions for demoralization should have specific objectives for different periods.</p>