It has been reported that medicinal mushrooms might induce different types of immune responses. Anthodia camphorata (A. camphorata) has attracted much attention for its therapeutic effects in treating hepatoma. We tested this anti-tumor effects using immunomodulation of macrophages and extracts of A. camphorata. We evaluated the anti-proliferation effects of various extracts of A. camphorata from fruiting bodies (AC-FB), mycelium of solid-state cultures (AC-SS), liquid-state cultures (AC-LS) and polyaccharide extracts from liquid-state cultures (AC-PS), and extracts of A. camphorata stimulated RAW 264.7 macrophage cell-conditioned mediums (MC-CMs). We measured cell proliferation and, did migration assays by cell cycle analysis and by observing apoptosis-related proteins (AKT, PARP-1, and NF-κB) and the mRNA expression of cytokines (TNF-α and IL-1β) of macrophages in human hepatoma cell lines. Our results revealed that two of the extracts (AC-FB and AC-SS) had better anti-proliferation effects, implying an immunomodulatory role the macrophages might play. This outcome is consistent with findings that AC-FB and AC-SS increase mRNA expression of TNF-α and the corresponding expression of apoptosis-related proteins on activation of MC-CMs, while A. camphorata polysaccharides induce macrophage-derived anti-tumor activities in human hepatoma cells via IL-1β and Akt activation. These results indicate that anti-tumor effects exerted by modulation of macrophage activation of A. camphorate may be influenced by the other constituents which (contained little or no polysaccharide) of A. camphorata.