Objective To investigate whether extracellular matrix metalloproteinase inducer (EMMPRIN) regulates autophagy in macrophages via the Toll-like receptor-4 (TLR4) pathway. Methods Human monocytic leukemia cell line (THP-1) monocytes were induced with phorbol ester (PMA) at a final concentration of 5 ng/ml for 48 h, and the successfully differentiated macrophages were tested. The cells were divided into the control group, EMMPRIN group and TAK-242 group. The expressions of TLR4, NF-κB, LC3-II, Beclin1 and P62 were detected by Western blot. The expressions of LC3-II, Beclin1 and P62 were detected by immunofluorescence. SPSS statistics 22.0 was used to process the data. Results Western blot showed that the EMMPRIN group had higher expression of TLR4, NF-κB, LC3-Ⅱ(P<0.05) than the control group and the TAK-242 group.Beclin1 protein expression level also increased in the EMMPRIN group, but with no significant difference compared with the control group (P>0.05), and with significant difference compared with the TAK-242 group(P<0.05). Expression of P62 were lower in the EMMPRIN group than the control group and the TAK-242 group(P<0.05). Expression of P62 were lower in the EMMPRIN group than the control group and the TAK-242 group (P<0.05). Immunofluorescence found that, the fluorescent expression of LC3-Ⅱ and Beclin1 protein were significantly higher in the EMMPRIN group than that in the control group and TAK-242 group (P<0.05), but the difference in the expression of P62 was not statistically significant. Conclusion EMMPRI may regulate excessive autophagy in human THP-1 macrophages through the TLR4 signaling pathway.