OBJECTIVES: To evaluate the effectiveness and cost-effectiveness of integrating seasonal malaria chemoprevention (SMC) with mass drug administration for helminth control among school-aged children living in communities where the burden of malaria and helminths is high in Ghana, West Africa. METHODS: This cluster randomised controlled trial will enrol 1200 children aged 5-10 years. Eligible children randomised to intervention clusters will receive SMC drugs (sulphadoxine-pyrimethamine plus amodiaquine) and anthelminthic drugs for soil-transmitted helminths-(albendazole), and for schistosomiasis (praziquantel), while children randomised to control clusters will receive SMC drugs alone. Pre- and post-intervention blood, urine and stool samples will be collected from children in both clusters. The effectiveness of the concomitant delivery will be determined by checking whether the combination of SMC and anthelminthic drugs prevents anaemia in the children randomised to the intervention clusters compared to the children in the control clusters. Cost analysis and cost-effectiveness of this integrated delivery approach will be determined by estimating the incremental costs and effects of co-administration of SMC drugs with mass drug administration of anthelminthic drugs compared to SMC alone, including cost savings due to cases of moderate and severe anaemia averted. EXPECTED FINDINGS: The findings of this study will provide evidence to inform public health recommendations for an integrated control of malaria and helminths among children living in the poorest countries of the world.