Encapsulation of synthesized triazole derivatives in the presence or absence of selenium nanoparticles (SeNPs) into nano-chitosan was directed to be employed in cancer treatment. The synthesized nano-capsules were well characterized using FTIR, TEM, SEM, DLS, and TGA. The results indicated that the nanoparticles exhibited a spherical shape with the size range of 80 nm as they were conjugated with triazole derivatives inside the capsules. These conjugated selenium nano-capsules showed enhanced thermal stability. The prepared Se nanoparticles were investigated for their anticancer activity and cytotoxicity toward the human colon cancer cell line (HCT116). The cytotoxicity and in vitro anticancer evaluation of the synthesized triazole derivatives loaded onto nano-chitosan through the samples (2a, 2b, 3a and 3b) have been assessed for human colon cancer cell line (HCT116). These samples are conjugated with selenium nanoparticles. They are loaded on nano-chitosan for the samples (3a and 3b) as well as nano-chitosan alone. The results showed that the in vitro antiproliferative activity of the newly synthesized compounds was significant and may be tested through further in vivo and pharmacokinetic studies.