PUFA status is highly implicated in cognitive development and metabolic disorder-related diseases. Genetic variants ofFADSgenes encoding enzymes that catalyze the rate-limiting steps of PUFA biosynthesis appear to be associated with n-3 and n-6 PUFA contents. Therefore, we conducted the first systematic review and meta-analysis to explore the association of the A-allele carriers of theFADS1rs174556 with PUFA status. The PRISMA guidelines were followed. The literature search was conducted up to November 2022 in PubMed, Web of Science, Embase, Cochrane Library, Airiti Library, and CINAHL. The Joanna Briggs Institute checklists were used to assess the methodological quality. The correlation with 95% CIs was determined by a random-effect meta-analysis. Eleven studies that met the inclusion criteria and acceptable quality were included in this systematic review. The data on PUFA contents were collected when they were mainly analyzed using blood samples and breast milk. Results of the meta-analysis on eight studies (one randomized controlled trial, one cohort study, and six cross-sectional studies) showed that the A-allele carriers of rs174556 were significantly negatively correlated with the concentrations of AA (P= 0.001), EPA (P= 0.004), and DHA (P= 0.025). However, ALA and LA were not associated with the A-allele carriers. To clarify the discrepancy, we further divided the studies into blood samples and breast milk subgroups. The subgroup analysis revealed that the A-allele carriers of rs174556 were significantly positively correlated with LA (P= 0.031) and negatively correlated with AA (P= 0.001), EPA (P= 0.036), and DHA (P< 0.001) in the blood sample group, but not in the breast milk group. The current meta-analysis proved that the A-allele carriers of theFADS1rs174556 appeared to be highly associated with lower concentrations of AA, EPA, and DHA but higher LA in the blood samples. The study has been registered on the International Prospective Register of Systematic Reviews (PROSPERO:CRD42022363978).Adv Nutr2023;x:xx–xx.