Here, the effect of morphology on the electrocatalytic activity of metal-organic framework (MOF) was investigated. Post synthetic gold (Au) insertion was done into hollow PCN-222 (HPCN-222) and solid PCN-222 (SPCN-222) frameworks by a simple hydrothermal method. The crystalline nature, chemical composition, and morphologies of the synthesized MOFs were characterized by PXRD, XPS, and TEM. Electrochemical characterizations were done by cyclic voltammetry and electrochemical impedance spectroscopy. The excellent electrocatalytic activity of highly small-sized Au(0) with the enhancement of electrical conductivity through a hopping mechanism combined with a hollow structure and high surface area in the HPCN-222 MOF hugely alters the electrochemical properties. Overall, a better electrocatalytic surface area, charge transfer coefficient, and catalytic activity were generated at the modified electrode. The hollow structure MOF showed better electrocatalytic activity than solid structured MOF. The AuHPCN-222 modified glassy carbon electrode (AuHPCN-222/GCE) electrochemical sensor was employed for the analytical analysis of estradiol (ED) in an optimum experimental condition. AuHPCN-222 showed selective and better electrocatalytic activity toward ED than GCE. The differential pulse voltammetric measurements by the fabricated sensor showed two linear determination ranges for ED; those are 0.01-1 and 1-220 μM. The measured limit of detection (m-LOD) was found to be 0.5 nM with the highest sensitivity of 2.2 μA μM cm-2. The analytical performances for the detection of ED in human urine and serum samples were done with reasonable recoveries (98%-103%) using the standard addition method. Also, the sensor showed better reproducibility and repeatability with stability.