Background Senile plaques and neurofibrillary tangles （NFTs） represent two of the major histopathological hallmarks of Alzheimer＇s disease （AD）. The plaques are primarily composed of aggregated amyloid β （Aβ） peptides. The processing of amyloid-β precursor protein （AβPP） in okadaic acid （OA）-induced tau phosphorylation primary neurons was studied. Methods Primary cultures of rat brain cortical neurons were treated with OA and β-secretase inhibitor. Neurons＇ viability was measured. AβPP processing was examined by immunocytochemistry and Western blotting with specific antibodies against the AβPP-N-terminus （NT） and AβPP-C-terminus （CT）. Results Ten nmol/L OA had a time-dependent suppression effect on primary neurons＇ viability. The suppression effect was alleviated markedly by pretreatment with β-secretase inhibitor. After OA treatment, both AβPP and β-C-terminal fragment （βCTF） were significantly increased in neurons. AβPP level was increased further in neurons pretreated with β-secretase inhibitor. Conclusions In OA-induced tau phosphorylation cell model, inhibition of β-secretase may protect neurons from death induced by OA. Because of increased accumulation of AβPP in neurons after OA treatment, more AβPP turns to be cleaved by β-secretase, producing neurotoxic βCTF. As a potential effective therapeutic target, β-secretase is worth investigating further.