Efficient removal of dissolved organic matter (DOM) is a challenge in advanced water/wastewater treatment, especially for high-molecular-weight polar or charged contaminants. Herein, we report a novel type of self-supported hybrid poly(vinylidene fluoride, PVDF) membrane incorporated with mesoporous carbon. It is fabricated via a simple organic-inorganic mixture and phase inversion process, in which the mesoporous carbon is used as an inorganic additive (up to 40 wt%) for the manipulation of polymeric pore structure and distribution, porosity, thickness, surface area and fouling characteristics. The hybrid membrane combines easy scaleup of polymers and large adsorption capacity of the mesoporous carbon. It possesses high surface areas (up to 550 m2 g-1), three-dimensionally interpenetrating porous structures, improved mechanical strength and chemical property, and favorable water flux (43 to 32 L m-2 h-1). The membrane with 25 wt% of mesoporous carbon shows the best separation performance for large-molecular-sized microcystin-LR (Mw = 995) and Rhodamine B (Mw = 479) (3.8 and 14.8 mg g-1, respectively). Moreover, the complementary properties allow the hybrid membrane be regenerated conveniently and reused with steady cyclic performance. This membrane-forming procedure demonstrates a trade-off relationship of thermodynamics versus kinetics. It is also affected simultaneously by particle-polymer interactions on the micron-sized interfaces during the phase inversion. Results suggest a promising route toward hybrid membranes for efficient sequestration of large-molecules of dissolved organic pollutants.