BackgroundDespite recent advances in therapy modalities of colorectal cancer (CRC), it is still the third cause of cancer-related deaths worldwide. Thus, the search for new target therapies became mandatory. DDR1 is a collagen receptor that has a suggested role in cellular proliferation, tumor invasion, and metastasis.Material and methodsForty-eight cases of CRC, 20 of CR adenoma, and 8 cases of non-tumoral colonic tissue were subjected to immunohistochemistry by DDR1 andβ-cateninantibodies. Results were compared among the different studied groups and correlated with clinicopathologic data and available survival data. Also, the expression of both proteins was compared versus each other. Results were compared among the 3 studied groups and correlated with clinicopathologic and survival data.ResultsIt revealed a stepwise increase of DDR1 expression among studied groups toward carcinoma (P= 0.006). DDR1 expression showed a direct association with stage D in the modified Dukes’ staging system (P= 0.013), higher-grade histologic types (P= 0.008), and lymph node invasion (P= 0.028) but inverse correlation with the presence of intratumoral inflammatory response (TIR) (P= 0.001). The shortest OS was associated with strong intensity of DDR1 (P= 0.012). The DDR1 andβ-cateninexpressions were significantly correlated (P= 0.028), and the combined expression of both was correlated with TNM staging (P= 0.017).ConclusionDDR1 overexpression is a frequent feature in CRC and CR adenoma. DDR1 is a poor prognostic factor and a suppressor of the TIR. DDR1 andβ-cateninseem to have a synergistic action.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12957-023-03041-6.