The invention discloses a laser cutting device of a light guide plate. The laser cutting device comprises a machine frame. The machine frame comprises a worktable and a supporting frame installed on the worktable, wherein a through hole is formed in the worktable; a vacuum adsorption plate is arranged in the through hole, and the bottom surface of the vacuum adsorption plate is fixed to a piston rod of a lifting air cylinder; a cutting mechanism is arranged on the bottom surface of the supporting frame and is connected with a dust removal mechanism; the cutting mechanism comprises a plurality of rectangular linear sliding rails fixed on the bottom surface of a horizontal plate; each linear sliding rail comprises four guide rail bodies connected end to end; the guide rail bodies of the multiple linear sliding rails are arranged correspondingly in parallel, and the lengths of the guide rail bodies are gradually decreased from outside to inside; each guide rail body is provided with a single saddle, wherein a guide groove of a laser cutter is formed in the upper end surface of the single saddle, and a positioning groove of the laser cutter is formed in the guide groove over the guide rail body. The laser cutting device of the light guide plate can meet the cutting requirements of light guide plates in different sizes, and effectively remove chips and dust generated in the cutting process.