To investigate induction of endoplasmic reticulum stress-mediated apoptosis in diffuse large B-cell lymphoma cells by p-coumaric acid. Methods Diffuse large B-cell lymphoma cell line OCI-LY1 was treated with pcoumaric acid (0, 0. 4, 0. 8, 1. 6 and 3. 2 mmol / L) and the inhibition rate and half-inhibition concentration ( IC50 ) was determined by CCK8 assays. Subsequently, groupings were set as follows: (1) control group and p-coumaric acid groups (1 / 2 IC50 , IC50 and 2 IC50 ). (2) control group, p-coumaric acid IC50 group, 4-PBA group (5 mmol / L) and 4-PBA+IC50 group. Cell activity was assessed by CCK8 assays. Apoptosis was detected by flow cytometry. Relative expression of GRP78, ATF6, CHOP, p-PERK and p-IRE1α proteins was detected by Western blot. Results p-Coumaric acid inhibited OCI-LY1 cell proliferation in a dose-dependent manner with an IC50 value of 2. 601 mmol / L. Compared with the control group, the cell inhibition rate, apoptosis, and GRP78, ATF6, CHOP, p-PERK and p-IRE1α protein expression were significantly increased in the 1 / 2 IC50 , IC50 and 2 IC50 groups ( P < 0. 01). Compared with the IC50 group, the cell inhibition rate, apoptosis and GRP78, ATF6, CHOP, p-PERK, p-IRE1α protein expression were significantly decreased in the 4-PBA group and 4-PBA+IC50 group (P<0. 01). Compared with the 4-PBA group, cell inhibition rate, apoptosis and GRP78, ATF6, CHOP, p-PERK and p-IRE1α protein expression were significantly increased in the 4-PBA+ IC50 group (P<0. 01). Conclusions p-Coumaric acid inhibits OCI-LY1 cell proliferation, possibly by activating endoplasmic reticulum stress and inducing apoptosis.