Background: Growing evidence indicates a correlation between colorectal cancer (CRC) and intestinal dysbiosis or colonization by single bacterial species such as Streptococcus gallolyticus (Sg), yet a causality link remains to be established. IL-8 is one of the pro-inflammatory and angiogenic cytokine which is frequently related to carcinogenesis. Objectives: This study was designed to assess the association between Sg colonization, IL-8 tissue levels and CRC development in Egyptian CRC patients. Methodology: Both tumour tissue (TU) and adjacent normal mucosa (NTU) were obtained from each patient of a total 35 CRC patients undergone surgical resection of CRC. Colonoscopical biopsies from normal colonic mucosa were also taken from 20 control subjects. Detection of Sg were done by both bacteriological and molecular (conventional PCR) methods from all tissue samples from both patients and control subjects. In addition, fecal samples were collected from both CRC patients and control subjects for assessing fecal Sg bacteria. Moreover, tissue level of IL-8 was measured by ELISA in all tissue samples from both patients and control subjects. Results: The molecular method revealed more positive results than the bacteriological method. The positive detection of fecal Sg was not significantly different between patients and control groups. Sg detected from TU and NTU colorectal tissues of CRC patients in a significantly higher rate than control group, however, the frequency of positively detected Sg in TU versus NTU tissues of CRC patients was not significantly different. There was no significant association between the positive detection of Sg and each of age and sex of patients, stage, grade, and location of tumors. For IL-8, tissue level was significantly higher in TU and NTU tissues of CRC patients when compared with control tissues, and was significantly higher in TU than in NTU tissues of CRC patients. Also, IL-8 tissue level was significantly higher in Sg+ve tissue samples than in Sg-ve tissue samples. There was a significant positive correlation between IL-8 tissue level and both stage and grade of the tumor. There was no significant difference in tissue levels of IL-8 regarding age and sex of patients nor the location of the tumor. Conclusion: Higher detection rate of Sg in CRC tissues than that of normal controls indicates a strong association between Sg and CRC development, and higher level of IL-8 in Sg +ve tissues than Sg –ve tissues indicates that IL-8 has a role in the association between this bacterium and CRC.