The effective index of the cladding fundamental space-filling mode in photonic crystal fiber (PCF) is simulated by the effective index method. The variation of the effective index with the structure parameters of the fiber is achieved. For the first time, the relations of the V parameter of Yb³⁺-doped PCF with the refractive index of core and the structure parameters of the fiber are provided. The single-mode characteristics of large-core Yb³⁺-doped photonic crystal fibers with 7 and 19 missing air holes in the core are analyzed. The large-core single-mode Yb³⁺-doped photonic crystal fibers with core diameters of 50 μm, 100 μm and 150 μm are designed. The results provide theory instruction for the design and fabrication of fiber.