© 2021 Boybeyi-Turer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Infantile hypertrophic pyloric stenosis (IHPS) is one of the hallmark pediatric surgical diseases. However, its etiology remains incompletely understood. By systematically reviewing the literature, we aim to clarify the effect of the effect of occupational and environmental factors and role of nitric oxide (NO) metabolism in the etiopathogenesis of IHPS. The systematic review is drafted with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement (PRISMA) and the Meta-analysis of Observational Studies in Epidemiology (MOOSE). Systematic literature search will be performed for the period 2000 (Jan) to 2020 (Dec) in the databases: MEDLINE, EMBASE, PubMed. The systematic search will cover the literature in English and Turkish language and will be limited to studies on human subjects. Four investigators will independently search the databases (MEDLINE, EMBASE, PubMed) according to the defined search strategy. The full-text of the selected articles will be screened independently by four reviewers, against the inclusion criteria. Descriptive data will be extracted from each study regarding: study details, methods, participants, outcomes and calculations of association for potential further statistical analysis. If meta-analysis could not be undertaken, systematic approach to analyzing the findings of included multiple studies will be described. Heterogeneity will be assessed by quantifying the inconsistency across studies using I2 statistic. Statistical analysis will be performed using Comprehensive Meta-Analysis Version 3.0 software. The p values lower than 0.05 will be considered statistically significant for all analyses.