The lipoxygenase inhibitor nordihydroguaiaretic acid, a natural product purified from Larrea divaricata and Guaiacum officinale, showed a marked capacity to induce differentiation of various human malignant tumor cell lines. Nordy, a derivative of nordihydroguaiaretic acid, has been shown to effectively inhibit the growth of malignant human tumors transplanted in mice. However, it is unknown whether Nordy plays an important role in inducing the differentiation effects of human papillomavirus (HPV)-16 subgenes-immortalized human endocervical cells H8. In this study, we showed that Nordy arrested H8 cells in the G0/G1 phase, promoted cell differentiation in morphology, downregulated the expression of HPV-16 E6 mRNA and nuclear antigen Ki67, and inhibited telomerase activity on HPV-16 subgenes-immortalized human endocervical cells H8. Taken together, Nordy could suppress proliferation by inhibiting proliferation-related events and promote cell differentiation in H8 cell. The results suggested that Nordy might be a potential tumor therapeutic agent.