Objective: To investigate the alterations of the cerebral resting-state spontaneous neural activity in colorectal cancer patients with depressive symptoms. Methods: Thirty-three colorectal cancer patients (patient group) with depression and 43 healthy subjects (control group) underwent the resting state functional magnetic resonance imaging (rs-fMRI). The amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) were calculated. Two independent samples t test were used to compare the ALFF and fALFF values between two groups by DPABI software, and then correlation analysis was performed between ALFF and fALFF with statistical significance and Patient Health Questionnaire (PHQ-9) scores and Generalized Anxiety Disorder (GAD-7) scores. Results: Compared with the control group, the patient group showed significantly lower ALFF and fALFF values in the bilateral precuneus, calcarine gyrus, lingual gyrus, left cuneus, superior, middle, inferior occipital gyrus and right fusiform gyrus (t=-5.730, P<0.05; t=-4.872, P<0.05). There were no significant correlations between the ALFF and fALFF values in these regions and PHQ-9 or GAD-7 scores (P>0.05). Conclusion Spontaneous decrease of neural activity in occipital and parietal lobes exists in colorectal cancer patients with depression at resting-sate, which may be a potential neurobiological marker.