Aim To investigate the effect of curcumin in reducing human umbilical vein endothelial cell (HUVEC) injury induced by lipocalin-2 and the possible mechanism. Methods Lipocalin-2 at different concentration (0, 5, 10, 20 μmol/L) and different time gradient (0, 24, 48 and 72 h) were added in HUVEC, CCK-8 assay and flow cytometry were used to detect proliferation and apoptosis of HUVEC, the contents of monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6) in HUVEC supernatant were determined by enzyme-linked immuno-sorbent assay (ELISA), lactic dehydrogenase (LDH) activities were determined by colorimetry, the expressions of p-p38 MAPK, Bax and Bcl-2 in HUVEC supernatant were determined by Western blot. 10 μmol/L curcumin and 25 μmol/L SB203580 were added into HUVEC to detect the effect of curcumin. Results Compared with the control group, lipocalin-2 could significantly restrain the proliferation of HUVEC, increased the apoptosis of HUVEC, the MCP-1, IL-6 contents and LDH activities in HUVEC supernatant and Bax/Bcl-2 rate (P＜0.05). Compared with lipocalin-2 group, curcumin and SB203580 could increase the proliferation of HUVEC, restrained the apoptosis of HUVEC, the MCP-1, IL-6 contents and LDH activities in HUVEC supernatant and Bax/Bcl-2 rate (P＜0.05). Conclusions Our findings indicated that curcumin could reduce HUVEC injury induced by lipocalin-2, the protective mechanism is related to the inhibition of p38 MAPK pathway.