The expression of HIV-1 coreceptors (CXCR4 and CCR5) on monocyte surface can be regulated by the ligand of CD14 (LPS), which stimulate the susceptibility of the cells to HIV-1. To investigate whether it exists potential association between CD14 and HIV-1 coreceptor CXCR4, we tested the impact of CD14-specific monoclonal antibodies (mAbs) upon CXCR4-dependent responses, such as SDF-induced chemotaxis and HIV Env-mediated membrane fusion. The anti-CD14 mAb TUK4 like CXCR4-specific mAb 12G5 could block SDF-induced chemotaxis of U937 cells in a dose-dependent manner, while another CD14-specific mAb UCHM-1 did not show any activity. More interestingly, syncytium assay indicated that only the CD14-specific mAb TUK4 inhibited HIV Env-mediated CXCR4-dependent cell fusion between U937 cells and HIV-1HXB2 Env transfected CHO cells distinctly, consistent with its activity against CXCR4-dependent chemotaxis. These results provided experimental evidence for existence of close association between CD14 and HIV coreceptor CXCR4 on human monocytic cells.