Introduction: Single nucleotide polymorphisms (SNPs) in ATP-binding cassette C2 (ABCC2) gene may lead to higher intracellular oxaliplatin accumulation in the dorsal root ganglia and thus increased risk of oxaliplatin-induced peripheral neuropathy (OXAIPN). Aim: to study the association between the SNPs rs1885301 G>A, rs4148396 C>T and rs3740066 C>T in ABCC2 gene and the incidence of OXAIPN in gastrointestinal cancer patients. Patients and Methods: The study was prospective cohort study carried out at the Clinical Oncology Department, Ain Shams University Hospitals. Eligible patients received FOLFOX6 and FOLFIRINOX for 8-12 cycles. The SNPs assessment was performed using Real-time PCR using Rotor gene Q (QIAGEN®) system. The patients were followed up with each cycle to assess the incidence and severity of OXAIPN and other common toxicities including diarrhea, vomiting and neutropenia. Results: One hundred and twenty patients were included in the study. The minor allele frequency for the SNPs rs1885301 G>A, rs4148396 C>T and rs3740066 C>T were 0.4 ,0.2 and 0.3 respectively. The current study showed no association between the three SNPs and the incidence and grade of OXAIPN with less than 50% of the participants reported grade III and IV peripheral neuropathy. A significant association was found between rs4148396 C>T and the occurrence of neutropenia where TT haplotype showed significant higher incidence of neutropenia compared to CC + CT. Conclusion: Further large sample size study is recommended to confirm the association between rs4148396 C>T and the incidence of neutropenia in Egyptian gastrointestinal cancer patients in different populations.