The invention belongs to the technical field of organic synthesis, and particularly relates to an oxadiazole-containing piperazine derivative as well as a preparation method and use thereof. The oxadiazole-containing piperazine derivative provided by the invention has the following structural formula (shown in the description), wherein R is one of o-chlorophenyl, phenmethyl, o-methoxyphenyl, p-methoxyphenyl, p-fluorophenyl, pyridyl, o-fluorophenyl, p-nitrophenyl, p-chlorophenyl, 2, 3-dichlorophenyl, 3, 4-dichlorophenyl, m-methoxyphenyl, diphenylmethyl or m-trifluoromethylphenyl. Oxadiazole having excellent anti-cancer activity is introduced into a phenyl piperazine ring, to prepare the oxadiazole-containing piperazine derivative provided by the invention; the oxadiazole-containing piperazine derivative has an obvious inhibitory effect on the growth of cancer cells; the oxadiazole-containing piperazine derivative is cheap in used raw material, simple and easy to get, has few reaction steps and high yield, is suitable for industrial production and is used for preparing anti-cancer drugs.