The invention discloses an organic-inorganic nanocomposite gel sealing agent and oil-based drilling fluid. The sealing agent used for the oil-based drilling fluid is organic-inorganic nanocomposite gel, and the synthetic raw materials of the organic-inorganic nanocomposite gel includes molybdenum disulfide, 2-ethyl acrylic acid, N, N-dimethylacrylamide and N,N-methylene bisacrylamide; the drilling fluid includes the organic-inorganic nanocomposite gel provided by the invention. The organic-inorganic nanocomposite gel is used as a nano sealing agent, the particle size distribution of the organic-inorganic nanocomposite gel is 50-200 nm, the organic-inorganic nanocomposite gel can effectively prevent drilling fluid filtrate from intruding into stratums and prevent accidents such as borehole wall collapse, the organic-inorganic nanocomposite gel is particularly suitable for nano-sealing of shale stratums, and the preparation method of the organic-inorganic nanocomposite gel is reliable in principle and has a wide market prospect.