ObjectiveTo systematically evaluate the efficacy of high-flow nasal cannula oxygen therapy (HFNC) versus standard nasal cannula oxygen therapy (SNC) in improving hypoxemia during non-intubated general anesthesia (NIGA) in obese patients. MethodsPubMed, Embase, Web of Science, The Cochrane Library, Wanfang Data, CNKI, VIP, and CBM were searched from database inception to March 2026. Two researchers screened the the literature, extracted data, and evaluated the risk of bias in the included studies independently. RevMan 5.4, Stata 15.1 and TSA 0.9.5.10 beta software were used for the meta-analysis and trial sequential analysis. Results A total of 13 RCTs were included, including 1 971 patients. The meta-analysis results showed that compared with the SNC group, the HFNC group reduced the incidence of hypoxemia (RR=0.19, 95%CI 0.07~0.48, P=0.000 4) and mask usage rate (Peto-OR=0.11, 95%CI 0.07~0.17, P<0.000 01), shortened the diagnosis and treatment operation time (MD=?1.78, 95%CI ?2.90~?0.65, P=0.002), but there was no statistically significant difference in the incidence of nasopharyngeal adverse reactions between the two groups (RR=0.55, 95%CI 0.19~1.62, P=0.28). Subgroup analysis showed that there was no statistically significant difference in the incidence of hypoxemia between the HFNC group (under non-pure oxygen conditions) and the SNC group (RR=0.89, 95%CI 0.53~1.50, P=0.67). ConclusionsHFNC can reduce the occurrence of hypoxemia and mask intervention during NIGA in obese patients, however, its effect may differ according to the FiO2 setting. Due to the limitations of the included research quality, more high-quality studies are needed to verify the above conclusions.