Dynamic finite element software ANSYS/LS-DYNA was used to set up a typical finite element model for Kiewitt8 single-layer reticulated shell which contained reticulated shell member, purlin hanger, purlin, rivet, roof boarding, wall and ground. The dynamic response of structure subjected to internal eccentric blast loading was studied by using ALE (Arbitrary-Lagrange-Euler) algorithm, four response types are defined, that is: No Impairment, Member Developing Plasticity, Large Deformation of Reticulated Shell and Destruction with explosion relief. The response rules of the structure under internal eccentric blast loading with different explosion point position, section size of reticulated shell member, rise-span ratio, supporting condition and thickness of roof boarding are obtained through the comparison of the plastic strain, the plastic development degree and displacement of structure. The result offers the theoretical basis for reasonable defense design of reticulated shell structure for resisting blast.