Objective: To compare the effects of breastfeeding and formula feeding on tissue oxygen saturation, hemoglobin concentration index and intestinal flora in full-term newborns. Methods: A total of 500 full-term newborns born in our hospital from June 2020 to December 2020 were selected as the research subjects and divided into a breastfeeding group (n=238) and a formula feeding group (n=262) according to different feeding methods. The growth and development indices (body weight, body length, head circumference), tissue oxygen saturation [cerebral tissue oxygenation index (cTOI), splanchnic tissue oxygenation index (sTOI)], hemoglobin concentration index [cerebral tissue hemoglobin index (cTHI), splanchnic tissue hemoglobin index (sTHI)] and intestinal flora (lactic acid bacilli, bifidobacteria) were detected and compared between the two groups. Results: There were no significant differences in body weight, length and head circumference between the two groups after 30 days of feeding (P>0.05), while the weight gain of breastfeeding group was significantly higher than that of formula feeding group (P<0.05). In breast-feeding group, cTOI increased significantly at first and decreased after feeding (P<0.05), while cTHI increased significantly during and after feeding (P<0.05). But the trend of cTOI, sTOI, cTHI, sTHI in formula feeding group was not statistically significant before, during and after feeding (P>0.05). Compared with the formula feeding group, the cTOI of breast feeding group was higher than that of formula feeding group during and after feeding, while the sTHI and sTOI were lower after feeding (P<0.05). Compared with the formula feeding group, the bifidobacterium level in the intestinal flora in the breastfeeding group was significantly higher (P<0.05). Conclusion: Compared with formula feeding, breastfeeding is beneficial to weight gain of newborns, and it can improve the level of cTOI and cTHI, and may help to improve the intestinal flora.