To　solve　the　Vehicle　Routing　Problem　with　Simultaneous　Pickup-Delivery　and　Time　Windows　(VRPSPDTW),　a　Discrete　Cuckoo　Search　(DCS)　algorithm　was　presented.　Based　on　the　standard　cuckoo　search,　the　current　nest　was　improved　by　using　intra-route　improvement　method　2-opt　move　and　inter-route　improvement　method　swap/shift　move　during　the　process　of　Lévy　flight　position　update,　and　a　new　nest　was　selected　randomly　by　using　intra-route　improvement　method　relocate/exchange　move　and　inter-route　improvement　method　GENE　move　during　the　process　of　nest　position　update.　The　performance　of　DCS　algorithm　was　tested　and　compared　with　genetic　algorithm　and　parallel-simulated　annealing　algorithm.　Computational　results　showed　that　the　proposed　DCS　was　able　to　achieve　the　Best　Known　Solution　(BKS)　as　100%　of　the　9　small-to-medium　instances.　For　the　large　scale　instances,　DCS　obtained　better　solutions　for　5　instances,　and　equaled　BKS　in　17　instances.　These　three　algorithms　were　compared　based　on　Friedman　test　and　Wilcoxon　signed-rank　test　with　Rank　value　method,　and　the　result　showed　that　DCS　was　an　effective　method　for　solving　VRPSPDTW　problem.　©　2018,　Editorial　Department　of　CIMS.　All　right　reserved.