In the study， a model of HeLa cells protected by Lactiplantibacillus plantarum CY1-2 against 2，2'-azobis[2-methylpropiona midine] dihydrochloride (ABAP) damage was established. The antioxidant mechanism of L. plantarum CY1-2 was investigated using cell proliferation test， morphological observation and western blot analysis. The results showed that the cell protective model conditions were as follows: 108 CFU/mL of L. plantarum CY1-2 protected cells for 3 h， and then 110 mmol/L of ABAP damaged cells for 3 h. Under this model condition， both the cell and the cell-free extract of L. plantarum CY1-2 could effectively improve the viability of HeLa cells， and the cell survival rate increased by 9.41% and 25.71%， respectively. Meanwhile， microscopic observation showed that compared with the injured group， HeLa cells protected by the cell-free extract of L. plantarum CY1-2 were large and plump， with clear edges and good extensiability. Western blot analysis indicated that， compared with the injured group， the cell-free extract of L. plantarum CY1-2 could positively regulate the expression of kelch-like ECH-associated protein 1 (Keap1)， nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1) proteins in HeLa cells， resulting in increasing by 18%， 47% and 58% respectively. L. plantarum CY1-2 protects HeLa cells from oxidative damage by activating Keap1-Nrf2-ARE signaling pathway to improve its antioxidant capacity. This study was expected to provide a theoretical basis for the development of lactic acid bacteria antioxidants.