Nickel is an essential plant micronutrient; however, even at low concentrations, it may be phytotoxic. Selenium is a beneficial element with an alleviating effect that has been confirmed in the case of many abiotic stresses, including metal toxicity. The aim of this study is to assess the effect of two forms of Se (Se(IV) or Se(VI)) on the phytotoxicity, accumulation, and translocation of Ni in lettuce. Nickel causes a reduction in lettuce growth and vitality of roots, probably through increased lipid peroxidation. The application of Se(IV) to a Ni-contaminated medium resulted in a further reduction of growth, especially in the presence of 6 µM Se(IV). The growth-promoting effect of Se was found only in the 2 µM Se(VI)/10 µM Ni treatment. The application of 6 µM Se, regardless of the Se form, to the Ni-containing substrate caused an increase in shoot Ni concentration. In turn, a decrease in root Ni content was found for all Se treatments. The strong aggravation of Ni phytotoxicity in the presence of 6 µM Se(IV) was most likely related to the accumulation of high Se concentration in the roots, and the combination of high root Ni accumulation caused irreversible dysregulation of cell metabolism.