Surfactant is one of the most important chemical entities in drug formulation which can bind with drug molecules. Herein, the binding interaction of ciprofloxacin hydrochloride (CFH) drug with two different surfactants (sodium dodecyl sulfate (SDS) and Triton X-100 (TX-100)) has been investigated through UV-Visible spectroscopic and cloud point measurement techniques at different conditions. The absorption spectrum of CFH was found to be dependent on presence of additives/temperature change. The binding constant (Kb) of CFH+SDS/CFH+TX-100 was found to be increased primarily, reached a maximum value and then decreased with the increase of temperature, except in water medium (pH=2.0) and 30% (v/v) methanol. The Kb values for CFH+SDS were found to be higher in the aqueous medium than almost all medium studied herein, while better binding was observed in the alcoholic medium in the case of the CFH+TX-100 system. The Gibbs free energy of binding (ΔGb o) for both CFH+SDS and CFH+TX- 100 systems were attained negative in each case studied, inferring the spontaneous binding phenomenon. The cloud point (CP) value of CFH+TX-100 mixture was lessened in ZnSO4Δ7H2O solution and the CP values exhibited a gradual reduction through the upsurge of electrolyte concentration. The positive values of the Gibbs free energy of clouding indicated the nonspontaneous clouding phenomena. To disclose the interaction between drug and surfactant, other thermodynamic parameters, e.g., enthalpy (ΔHb o) and entropy (ΔSb o), different transfer energies as well as entropyenthalpy compensation parameters of binding/clouding were evaluated and clarified with proper explanation.