Tumor-targeting delivery of drugs has received much attention in the field of drug development. Traditional antitumor agents are often nonspecific for tumor cells; therefore, tumor-targeting drug-delivery design is a promising approach to improve the therapeutic efficacy of chemotherapy. Polyunsaturated fatty acids (PUFAs), such as linoleic acid, α-linolenic acid, arachidonic acid and docosahexaenoic acid, are naturally occurring essential substances which play important roles in cell growth. Due to their lipophilic nature, PUFAs are readily incorporated into the lipid bilayer of cells, especially tumor cells. Therefore, PUFAs can be used as an applicable carrier to increase the therapeutic efficacy of anticancer drugs. In this review, several PUFA-drug conjugates with potent antitumor activities are summarized, and the bright prospects of PUFAs in drug development are also proposed. A general design strategy of PUFA-drug conjugates is provided, as well as a discussion of the recent progress in PUFA-drug conjugates and preclinical therapies. The tumor growth-related PUFAs are expected to play an important role in the development of more efficacious antitumor agents.