Ethylene response factor (ERF) genes have been involved in responses to biotic and abiotic stress, including hypoxia and anaerobic stress. Vacuum packaging (a typical anaerobic stress) is an effective storage method used to delay browning of fresh-cut lotus root (Nelumbo nucifera). In model plants, ERF genes have been identified as responsive to hypoxia. Whether ERF is associated with browning of vacuum-packaged lotus root has not been studied. The effects of vacuum packaging on browning, phenolic content, the enzyme activity of phenylalanine ammonia lyase (PAL), polyphenol oxidase (PPO), and peroxidase (POD), and PPO, PAL, POD, and ERF genes expression in fresh-cut lotus root were studied. Downregulation of NnPAL1, NnPPOA, and NnPOD2/3 attributable to vacuum packaging coincided with increased related enzyme activities and the degree of browning of fresh-cut lotus root. The expression patterns of NnERF4/5 were consistent with the changes in NnPAL1, NnPPOA, and NnPOD2/3 gene expression. It has been proposed that NnERF4/5 could have be important regulators of fresh-cut lotus root browning, and that the relationships of NnERF4/5 and NnPAL1, NnPPOA, and NnPOD2/3 should to be studied further.