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Microplastics pollution has gained much attention for its harmful impact on aquatic organisms. This study aimed to evaluate the size-effects and concentration-effects of microplastics on the physiology of hybrid snakehead (Channa maculate × Channa argus). Parameters including antioxidant enzyme activities, intestinal morphology, immune-related genes, and oxidative-stress-related genes were tested in two life stages development. The results showed hybrid snakehead larvae (0.057 ± 0.009 g in weight) were more intolerant to high concentrations of small-sized microplastics. Hybrid snakehead juvenile (3.87 ± 1.19 g in weight) had been stimulated the immune response and triggered antioxidant defenses under the exposure stress. There were differential expressions of inflammatory and oxidative-stress-related genes coping with differential sizes and concentrations of microplastics. High concentrations of microplastics (2 mg/L, 20 mg/L) stimulated more severe immune response and shortened intestinal villi. In addition, the damaged intestinal morphology and function did not recover after 48 h of depuration. This work is expected to provide a meaningful perspective for better understanding the size and concentration dependent effects and life-stage specific effects of microplastics in hybrid snakehead.