Growing selenium (Se)-biofortified alternative crops in saline and Se-contaminated agricultural land in arid/semi-arid regions, such as the western United States, depends upon the plant’s ability to tolerate high salinity and accumulate Se. In this field study, we evaluated the ability of five prickly pear cactus clones [Opuntia ficus-indica (L.) Mill., no. 243, 248, 250, 252, and 255] to grow, accumulate and volatilize Se from drainage sediment high in sulphate salinity (∼5 dS/m), soluble B (∼5 mg/L) and Se concentrations (∼0.8 mg/L). After 3 years of growth, all clones exhibited significant decreases up to 20% in height and fruit production compared with control clones. Mean Se concentrations (mg/kg DM) ranged from 4.9 to 9.8 in cladodes, 1.5–2.5 in fruit flesh, and 4.5–10.1 in seeds. Rates of Se volatilization varied from 20 to 80 μg Se/m2 per day among the tested clones. The successful growth of prickly pear cactus and its accumulation and volatilization of Se under adverse soil conditions may provide growers with an alternative Se-biofortified crop in the westside of the San Joaquin Valley in central California.