In this study, biosorption processes performed with and without ultrasound-assisted were presented for the first time comparatively. For this purpose, the potential for use of Ulva lactuca Linnaeus 1753 (U. lactuca) which is a macroalgae, as an alternative biosorbent was investigated for Hg(II) removal from aqueous solutions. Both conventional univariate and multivariate methods were evaluated to optimise biosorption processes. Biosorption equilibrium time was determined as 60 min for without ultrasound-assisted method, while it was only 3 min for ultrasound-assisted method. Biosorption processes were optimised by Central Composite Design (CCD) and successfully described by quadratic polynomial models as a function both of R (%) and qe (mg/g). In optimum conditions (Co = 125 mg/L, m = 30 mg, pH = 4.0 for ultrasound-assisted method and pH = 2.0 for without ultrasound-assisted method), removal efficiencies were achieved experimentally as 95.8% +/- 0.2 and 96.1% +/- 0.7 (N = 2), respectively. Models with high regression coefficients (R-2(adj) > 95%) obtained from Response Surface Methodology (RSM) were found to be applicable to the estimation of biosorption data. Biosorption equilibrium data was defined by Langmuir model. Langmuir's maximum sorption capacity was increased from 125.6 to 232.0 mg/g when ultrasound-assisted method was applied. According to the results of kinetics evaluation, both biosorption processes were thermodynamically possible, endothermic (Delta Ho>0) and spontaneous reactions (Delta Go<0) controlled by chemisorption based on the pseudo-second-order kinetic models. Results showed that ultrasound-assistance to the biosorption process contributed positively to increasing the rate of reaction and allowing sorption to be completed in a shorter time by facilitating sorption mass transfer.