Discrete hole film cooling has been commonly used as an effective cooling technique to protect gas turbine blades from hot gas. There have been numerous investigations on the cylindrical hole and shaped hole, but few experimental investigations on the cooling mechanism of the novel film holes with side holes (anti-vortex hole and sister hole) are available. This paper presents an experimental and numerical investigation to study the film cooling performance and flow structure of four kinds of film holes (cylindrical hole, fan-shaped hole, anti-vortex hole and sister hole) on the flat plate. The film holes have the same main hole diameter of 4mm and the same inclination angle of 45°. The adiabatic film cooling effectiveness is obtained by the steady-state Thermochromic Liquid Crystal (TLC). The flow visualization experiment and numerical investigation are performed to investigate the flow structure and counter-rotating vortex pair (CRVP) intensity. The smoke is selected as the tracer particle in the flow visualization experiment. The mainstream Reynolds number is 2900, the blowing ratio ranges from 0.3 to 2.0, and the density ratio of coolant to mainstream is 1.065. Experimental results show that compared with the cylindrical hole, the film cooling performance of the anti-vortex hole and sister hole shows significant improvement at all blowing ratios. The sister hole can achieve the best cooling performance at blowing ratios of 0.3 to 1.5. The fan-shaped hole only performs well at high blowing ratios and it performs best at the blowing ratio of 2.0. Flow visualization experiment and numerical investigation reveal that the anti-vortex hole and sister hole can decrease the CRVP intensity of the main hole and suppress the coolant lift-off because of side holes, which increases the film coverage and cooling effectiveness. For the sister hole, the side holes are parallel to the main hole, but for the anti-vortex hole, there are lateral angles between them. The coolant interaction between the side holes and main hole of the sister hole is stronger than that of the anti-vortex hole. Therefore, the sister hole provides better film cooling performance than the anti-vortex hole.