Fatigue tests were conducted on two kinds of vulcanised natural rubber with different formulas under uniaxial and multiaxial loading. The results reveal that interfacial adhesion of material A is better, and compared with material B, fatigue life of material A is longer. Under the same engineering strain amplitude, lower fatigue life under tension-torsion non-proportional loading is due to the increase in total hysteresis energy in the torsional direction. Scanning electron microscopy analysis showed that fatigue failure is related to ligaments breakage for material B, while cavitation induced by the decohesion between zinc oxides and rubber matrix is the main cause of the fatigue damage for material A.