Fungal immunomodulatory protein (FIP) is a novel functional protein family with specific immunomodulatory activity identified from several macro-fungi. A variety of biological activities of FIPs have been reported, such as anti-allergy, anti-tumor, mitogenic activity, and immunomodulation. Among all known FIPs, the firstly discovered FIP was isolated from Ganoderma lucidum, and most FIP members were from Ganoderma genus. Compared with other FIPs, Ganoderma FIPs possess some advantageous bioactivities, like stronger anti-tumor activity. Therein, gene sequences, protein structural features, biofunctions, and recombinant expression of Ganoderma FIPs were summarized and addressed, focusing on elucidating their anti-tumor activity and molecular mechanisms. Combined with current advances, development potential and application of Ganoderma FIPs were also prospected. KEY POINTS: • More than a dozen of reported FIPs are identified from Ganoderma species. • Ganoderma immunomodulatory proteins have superior anti-tumor activity with promising prospects and application. • Current review comprehensively addresses characterization, biofunctions, and anti-tumor mechanisms of Ganoderma FIPs.