Environmental exposure to lead (Pb) is reported to associate with the development of Alzheimer's disease, where the formation of β-amyloid peptides (APs) of (1-40), (1-42), and (25-35) is considered as the major risk factor. In this context, we aimed at investigating the effect of epigallocatechin gallate (EGCG), a major flavonoid polyphenol available in green tea, in mitigating the individual and combined toxicity generated by Pb and β-APs in terms of oxidative stress and apoptosis in human neuronal cells. SH-SY5Y cells were exposed to Pb and β-APs of (1-40) and (25-35) individually and in different combinations in the presence and absence of EGCG. The results indicated that EGCG mitigated both Pb- and β-AP-induced oxidative stress in scavenging reactive oxygen species and apoptosis by improving the expression levels of Bax and bcl2 and inhibiting annexin V and caspase-3. Thus, our study shows that EGCG protects SH-SY5Y cells against the cytotoxicity induced by Pb and β-APs by decreasing oxidative stress and inhibiting apoptosis.,? 2019 Wiley Periodicals, Inc.