Helicobacter pylori (H. pylori) infection is not limited only to gastrointestinal tract but also associated with various extra-gastric diseases including colorectal cancer (CRC). This work aimed to estimate H. pylori impact on extracellular-matrix deposition in CRC-patients. Methods: A total of 285 CRC patients and 120 healthy individuals were included. H. pylori-antigen and fibronectin were quantified in patients’ sera by ELISA. Results: Our findings showed that H. pylori-infected patients were more susceptible for developing severe tumour features than those without. Patients with late stages (III–IV) and poor tumor differentiation (G3-G4) displayed 7.3 and 11.5-fold increase in H. pylori-antigen than with early stages and low grades, respectively. The results showed that patients infected with H. pylori were accompanied by significant increase in fibronectin compared to those without. Indeed, the risk of elevated fibronectin for developing severe tumor features (late stages and high tumor grades) was 2.3 and 3.4, respectively, in cases of low H. pylori-antigen concentration. Surprisingly, this risk was increased yielding an estimated odds ratio of 5.1 and 15.4 in case of high H. pylori-antigen concentration. Conclusions: Our findings could indicate the influence of H. pylori on enhancing extracellular-matrix deposition subsequently increases patients’ susceptibility for developing severe tumor features.