The application of selenium (Se) fertilizer not only promotes crop growth but also meets the human demand for Se by increasing the Se content in food. However, the application of nanosized selenium (nano-Se) in hybrid rice (Oryza sativa L.) production has not been reported. Therefore, the present study conducted a field experiment to investigate hybrid rice’s performance under the different application modes of nano-Se. The nano-Se solution was foliar-applied: once at the end of the tillering (S1), heading (S2), and grain-filling (S3) stages or twice at the end of the tillering stage and the heading stage (S4), and at the end of the tillering stage and the grain-filling stage (S5). The treatment without Se application was taken as the control (CK). The results showed that compared with CK, the S1, S2, S3, S4, and S5 treatments increased the grain yield by 27.83–40.60%, 16.06–25.95%, 14.78–40.86%, 20.94–43.79%, and 22.41–43.52%, respectively. The highest or equally highest grain yield was recorded in the S1 treatment. Yield-related traits including the effective panicle number, grain number per panicle, seed-setting rate, and 1000-grain weight significantly increased under nano-Se treatments. Compared with CK, nano-Se treatment increased the SPAD value (chlorophyll content), net photosynthetic rate, and dry matter accumulation by 3.82–32.83%, 2.85–59.55%, and 8.09–55.29%, respectively. An 11.51–572.85% higher grain Se content was recorded in nano-Se treatments than CK. Moreover, nano-Se application significantly enhanced the activity of superoxide dismutase and catalase. In conclusion, the foliar application of nano-Se enhanced the growth and yield formation of hybrid rice plants, and the S1 treatment was considered as the best application due to having the highest yield.