In this study, some electronic, hydrophobic and termochemical parameters of 28 different 5,8-quinolinequinones derivatives having diversity substituents have been calculated by using DFT (B3LYP) / 6-31G (d, p) method and basis set. Relationships between different molecular descriptives have been studied with used like molecular polarizability (α), dipole moment (μ), EHOMO, ELUMO, molecular volume (Vm), ionization potential (IP), electron affinity (EA), electronegativity (χ), molecular hardness (η), molecular softness (S), electrophilic index (Ꞷ), molar refractivity (MR), octanol–water partition coefficient (logP), thermochemical properties (entropy (Se), capacity of heat (C)); as to investigate activity relationships with molecular structure. In addition, The QSAR/QSPR between molecular properties and biological activity (Anti-proliferative and Anti-inflammatory activity) has investigated, where R, R2, F and P have taken into account in order to find a statistically correct model in QSAR studies. The dependence of the electronegative parameter on both electronic and thermochemical parameters was the most correlated parameter.