We investigate the crystal structure and physical properties of 2,4- and 3,4-dihydroxybenzaldehyde-4-nitrophenylhydrazone (DHNPH) isomer crystals to understand the relation between molecular ordering with noncovalent interactions based on phenolic OH groups. The microscopic and macroscopic optical nonlinearities of 2,4- and 3,4-DHNPH crystals are investigated experimentally and theoretically by using density functional theory calculations. Although the two isomer crystals possess a very similar molecular orientation based on a similar supramolecular synthon, 2,4-DHNPH exhibits a 1.7 times larger powder second harmonic generation efficiency than 3,4-DHNPH, which is attributed to their different intermolecular interactions involving phenolic OH groups. We show that the microscopic nonlinearity of the DHNPH molecules is particularly sensitive to variations in phenolic OH characteristics such as the orientation and intermolecular interactions.