A novel tetrahydrofuran derivative, trigonohowine (1), together with five known tetrahydrofuran derivatives(2–6), were isolated from the stems and leaves of Trigonostemon howii. The structure of 1 was elucidated byextensive spectroscopic methods and the known compounds were identified by comparisons with the data re-ported in literature. Among them, trigonohowine (1) represents the first example of a new type of tetra-hydrofuran derivative, possessing an unprecedented carbon skeleton containing 23 carbon atoms on the carbonskeleton and the known compouds (2–6) are rare tetrahydrofuran derivatives in the plant kingdom with variouscarbon skeletons. All isolated compounds were evaluated for their anti-HIV-1 activities. Compounds 1–6 showedsignificant anti-HIV-1 activities with EC 50 ranged from 0.08 to 1.03 µM. These findings suggest that the dis-coveries of these tetrahydrofuran derivatives with significant anti-HIV-1 activities isolated from T. howii could beof great importance to the development of new anti-HIV agents.