Objective Previous studies have shown that dispositional mindfulness is associated with less psychological symptoms in cancer patients. The present study investigated how dispositional mindfulness is related to psychological symptoms in advanced gastrointestinal cancer patients by considering the roles of self‐acceptance and perceived stress. Methods A total of 176 patients with advanced gastrointestinal cancer were recruited to complete a series of questionnaires including Mindfulness Attention Awareness Scale, Self‐acceptance Questionnaire, Chinese Perceived Stress Scale, and General Health Questionnaire. Results Results showed that the proposed model fitted the data very well (χ2 = 7.564, df = 7, P = .364, χ2/df = 1.094, Goodness of Fit Index (GFI) = 0.986, Comparative Fit Index (CFI) = 0.998, Tucker Lewis Index (TLI) = 0.995, Root Mean Square Error of Approximation (RMSEA) = 0.023). Further analyses revealed that, self‐acceptance and perceived stress mediated the relation between dispositional mindfulness and psychological symptoms (indirect effect = −0.052, 95% confidence interval = −0.087 ~ −0.024), while self‐acceptance also mediated the relation between dispositional mindfulness and perceived stress (indirect effect = −0.154, 95% confidence interval = −0.261 ~ −0.079). Conclusions Self‐acceptance and perceived stress played critical roles in the relation between dispositional mindfulness and psychological symptoms. Limitations, clinical implications, and directions for future research were discussed.