[Display omitted] • Solubility of 1-[4-(4-hydroxyphenyl)piperazin-1-yl]ethenone (1-HPE) was studied. • The 1-HPE solubility was correlated by six thermodynamic models. • Hansen solubility parameters was used to evaluate the solubility behavior of 1-HPE. • Thermodynamic properties (Δ dis G , Δ dis S , Δ dis H) was calculated by the UNIQUAC model. The mole fraction solubility of 1-[4-(4-hydroxyphenyl)piperazin-1-yl]ethenone (1-HPE) in twelve mono-solvent systems namely "2-methoxyethanol (2-ME), methanol (MeOH), ethanol (EtOH), butan-1-ol (n -BuOH), 2-propoxyethanol (2-PE), propan-2-ol (i -PrOH), 2-methylpropan-1-ol (i -BuOH), Acetonitrile (MeCN), ethane-1,2-diol (EG), 2-ethoxyethanol (2-EE), propan-1-ol (n -PrOH), 2-butoxyethanol (2-BE)" were determined from 283.15 K to 323.15 K under 0.1 MPa. The experimental solubility order follows: 2-ME > 2-EE > 2-PE > 2-BE > MeOH > EtOH > n -PrOH > i -PrOH ≈ n -BuOH > i -BuOH ≈ MeCN > EG. The UNIQUAC model, modified Apelblat model, NRTL model, Wilson model, Jouyban model and NRTL-SAC model equation were used to correlate of 1-HPE solubility, and the average 104 RMSD of them was 0.89, 1.21, 0.94, 4.72, 0.60 and 1.25, respectively. Furthermore, Hansen solubility parameters analysis (HSP) was used to evaluate the miscibility of 1-HPE in the selected solvents. Hirshfeld surface (HS) analysis was performed to discuss the electrostatic features and the patterns of intermolecular interactions of 1-HPE. Thermodynamic properties (Δ mix G , Δ mix S , Δ mix H , Δ dis G , Δ dis S , Δ dis H) were calculated by the UNIQUAC model. The calculated results indicated that the dissolution and mixing process of 1-HPE in the mono-solvents selected in this work was spontaneous and entropy increment. [ABSTRACT FROM AUTHOR]