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Objective To analyze the clinical characteristics of neonatal lactic acidosis and thrombocytopenia induced by multi-oil fat emulsions （SMOF）， aiming to deepen clinicians’ understanding of adverse reactions to this drug. Methods Clinical data of two male neonates who suffered from lactic acidosis and/or thrombocytopenia after using intravenous SMOF for more than two weeks were analyzed. Literature review was conduced from PubMed， SinoMed， CNKI， Wanfang Data and CMAPH using the keywords of “neonate”， “multi-oil fat emulsions”， “lactic acidosis”， and “thrombocytopenia” in both Chinese and English. Clinical data of retrieved cases were collected and analyzed. Results Blood lactate， acidosis， and platelets returned to normal in two cases after terminating SMOF. Eight cases of fat overload syndrome caused by fat emulsion injection were retrieved by literature review， and one of them was treated with SMOF. All eight cases were improved after terminating intravenous fat emulsion， and four of them also received blood exchange therapy. Conclusions SMOF can cause neonatal lactic acidosis and/or thrombocytopenia. Clinicians should deepen the understanding of adverse reactions to this drug and lower the misdiagnosis and mistherapy rates.