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<b>Background:</b> The purpose of the study was to determine whether contrast-enhanced CT texture features relate to, and can predict, the presence of specific genetic mutations involved in CRC carcinogenesis. <b>Materials and methods:</b> This retrospective study analyzed the pre-operative CT in the venous phase of patients with CRC, who underwent testing for mutations in the KRAS, NRAS, BRAF, and MSI genes. Using a specific software based on CT images of each patient, for each slice including the tumor a region of interest was manually drawn along the margin, obtaining the volume of interest. A total of 56 texture parameters were extracted that were compared between the wild-type gene group and the mutated gene group. A <i>p</i>-value of <0.05 was considered statistically significant. <b>Results:</b> The study included 47 patients with stage III-IV CRC. Statistically significant differences between the MSS group and the MSI group were found in four parameters: GLRLM RLNU (area under the curve (AUC) 0.72, sensitivity (SE) 77.8%, specificity (SP) 65.8%), GLZLM SZHGE (AUC 0.79, SE 88.9%, SP 65.8%), GLZLM GLNU (AUC 0.74, SE 88.9%, SP 60.5%), and GLZLM ZLNU (AUC 0.77, SE 88.9%, SP 65.8%). <b>Conclusions</b>: The findings support the potential role of the CT texture analysis in detecting MSI in CRC based on pre-treatment CT scans.