Light plays an important role in plant growth, development, and response to environmental stresses. To investigate the effects of light on the plant responses to cadmium (Cd) stress, we performed a comparative physiological and proteomic analysis of light- and dark-grown Arabidopsis cells after exposure to Cd. Treatment with different concentrations of Cd resulted in stress-related phenotypes such as cell growth inhibition and decline of cell viability. Notably, light-grown cells were more sensitive to heavy metal toxicity than dark-grown cells, and the basis for this appears to be the elevated Cd accumulation, which is twice as much under light than dark growth conditions. Protein profiles analyzed by 2D DIGE revealed a total of 162 protein spots significantly changing in abundance in response to Cd under at least one of these two growing conditions. One hundred and ten of these differentially expressed protein spots were positively identified by MS/MS and they are involved in multiple cellular responses and metabolic pathways. Sulfur metabolism-related proteins increased in relative abundance both in light- and dark-grown cells after exposure to Cd. Proteins involved in carbohydrate metabolism, redox homeostasis, and anti-oxidative processes were decreased both in light- and dark-grown cells, with the decrease being lower in the latter case. Remarkably, proteins associated with cell wall biosynthesis, protein folding, and degradation showed a light-dependent response to Cd stress, with the expression level increased in darkness but suppressed in light. The possible biological importance of these changes is discussed.