Mutants of recombinant immunoregulatory protein of Ganoderma lucidum (rLZ-8) and applications thereof are provided. It is found by the present invention that: an anti-EGFR (epidermal growth factor receptor) domain exists in a structure of the rLZ-8; particularly, the domain through positive potential characteristics thereof induces a killing effect to an abnormal EGFR-expressed tumor. Based on the above scientific discovery, with utilizing computational simulation technology, the mutants of the rLZ-8, having better antitumor effects, are obtained.