A series of experiments dealing with variable secondary-side cooling conditions have been conducted at the IIST facility, including the natural circulation experiments under the secondary-side conditions of normal feed water, loss of feed water, and full of air. Different cooling conditions at the secondary side directly affect the primary-to-secondary heat transfer and then may influence the heat removal capability of natural circulation in the primary system. The corresponding analytical work is performed using the RELAP5/ MOD3 code. Good agreement is reached both qualitatively and quantitatively between the experimental data and calculated results, demonstrating the satisfactory assessment of RELAP5/MOD3 code compared with the IIST natural circulation experiments. The cooling conditions at the secondary side have no significant effect on the heat removal capability of natural circulation as long as sufficient coolant exists on the steam generator secondary side, based on current IIST data and analytical results. Continuous increase of the core temperature and system pressure is also demonstrated experimentally and analytically in the test with the secondary side dry for the sake of deficient heat transfer capability at the steam generator secondary system.