Five previously undescribed lanostane triterpene compounds (1-5) and nine known compounds (6-14) were isolated from Poria cocos. Their structures were elucidated through comprehensive 1D and 2D NMR spectroscopy, along with mass spectrometric analysis, experimental and calculated (ECD) spectra, and other complementary methods. The absolute configuration of compound 3 was determined via X-ray crystallography, supported by experimental and calculated electronic circular dichroism (ECD) data. All isolated compounds were evaluated in vitro for their anti-asthmatic activity in C48/80-induced degranulation of RBL-2H3 cells. The results showed compounds 1-3, 5-10 and 12-14 significantly inhibited the release of β-Hex (P < 0.05) and attenuated the degranulation process in RBL-2H3 cells at 10.0 μM. It is proposed that they may exert anti-asthmatic effects by inhibiting mast cell degranulation.