Cotton (Gossypium hirsutum L.) is a well-known and economically most beneficial crop worldwide while nickel (Ni) toxicity is a widespread problem in crops grown on Ni-contaminated soils. We investigated the response of silicon (Si) in cotton under Ni stress with respect to growth, biomass, gas exchange attributes, enzymatic activities, and Ni uptake and accumulation. For this, plants were grown in hydroponics for 12 weeks with three levels of Ni (0, 50, and 100 µM) in the presence or absence of 1 mM Si. Results showed that Ni significantly reduced the plant growth, biomass, gas exchange attributes, and pigment contents while Si application mitigated these adverse effects under Ni stress. Nickel stress significantly decreased antioxidant enzymes’ activities while increased malondialdehyde (MDA), hydrogen peroxide (H2O2), and electrolyte leakage (EC) in leaves and roots. The application of Si enhanced the activities of antioxidant enzymes and reduced MDA, H2O2, and EC in plants. Nickel application significantly increased Ni concentration and accumulation in leaf, stem, and roots while Si application significantly decreased Ni in these plant parts. The present study indicates that Si could improve cotton growth under Ni stress by lowering Ni uptake and reactive oxygen species (ROS) and by increasing antioxidant enzymes activities.