Background: Delirium is commonly encountered among hospitalized patients. It leads to cognitive and functional decline, resulting in longer recovery time. Patients with cancer, especially those undergoing surgery, are at higher risk for delirium and its adverse effects. Our study aims to explore the impact of delirium on hospitalized patients with colorectal cancer. Methods: We utilized the 2020 National Inpatient Sample (NIS) Database in conducting this retrospective cohort study. We identified patients with colorectal cancer and delirium using appropriate ICD-10 diagnostic codes. We stratified patients with colorectal cancer based on the presence or absence of delirium. A survey multivariable logistic and linear regression analysis was used to calculate adjusted odds ratios (ORs) for the primary and secondary outcomes. A p value of < 0.05 was considered statistically significant. The aim of this study was to investigate the impact of delirium on in-hospital mortality, hospital length of stay (LOS), and total hospitalization charge among hospitalized patients with colorectal cancer. Results: We identified a total of 77130 hospitalized patients with colorectal cancer, of which 1.91% (1475/77130) had concomitant delirium. The overall in-hospital mortality among patients with colorectal cancer was 2.74% (2115/77130). Among those with concomitant delirium, the mortality rate was significantly higher at 10.51% (155/1475, p < 0.001). Utilizing a stepwise survey multivariable logistic regression model that adjusted for patient and hospital level confounders, delirium was found to be an independent predictor of increased in-hospital mortality (adjusted OR 3.34; 95% (confidence interval [CI], 2.05-5.42; p < 0.001), longer LOS (coefficient 4.72; CI 3.26-6.18; p < 0.001), and higher total hospitalization charge (coefficient $36247; CI $22123- $50371; p < 0.001). Conclusions: Our analysis showed that delirium significantly worsens outcomes, including increased in-hospital mortality, LOS, and cost of healthcare utilization among hospitalized patients with colorectal cancer. Efforts should be made to prevent and proactively manage delirium in the inpatient setting, particularly with non-pharmacological techniques. Further prospective studies are needed to better describe these associations.