Objective: Colorectal cancer, frequently seen among gastrointestinal cancers, is one of the major causes in mortality and morbidity worldwide. In this study, we aimed to investigate the expression levels of RYBP and MDM2 genes in colorectal cancer. We further examined the possible correlation between RYBP and MDM2 expressions in colorectal cancer and the relationship between the expression of these genes and the clinicopathological features of patients with colorectal cancer. 
 Materials and Methods: In this study, fresh tumor colon/rectum tissues and the adjacent healthy tissues collected from 43 patients with colorectal cancer during a surgical operation. RYBP and MDM2 mRNA expressions were examined using Real-Time PCR. 
 Results: In this study results showed that the expression levels of both RYBP and MDM2 were decreased in tumor tissues compared to normal tissues with colorectal cancer patients, but these decreases were not statistically significant (p=0.673 and p=0.721, respectively). Moreover, while there was no correlation between RYBP and MDM2 mRNA expressions in colorectal cancer, no statistically significant relationship was found between the expressions of these genes and clinicopathological data (p>0.05). 
 Conclusion: Consequently, it can be said that RYBP and MDM2 expressions are not related to colorectal cancer, however, future studies with larger sample groups are needed to validate the results obtained from this study.