Rockwool (RC) and peat are two common substrates used worldwide in horticultural crop production. In recent years environmental and ecological concerns raised the demand for reducing the use of RC and peat. Although coconut coir (CC) has been increasingly used as an alternative to RC and peat, it is still needed to comprehensively evaluate the feasibility of CC before widely used. To meet this need, CC, RC, and peat-vermiculite (PVC) cultivations were used as tomato cultivation substrates to evaluate their effects on EC, pH and mineral ions in root-zone solution and drainage, nutrient uptake by crops, nutrient balance of cultivation system, plant growth and fruit quality. In general, CC significantly increased K and S uptake by crops, photosynthesis, individual fruit weight and total fruit yield compared to RC, and increased P and K uptake by crops and total fruit yield compared to PVC. Moreover, CC significantly increased organic acid of fruit in first truss compared to both RC and PVC. The uncredited nutrient was overally lower under CC than under RC and PVC (the lower, the better). For all substrates, the blossom-end rot (BER) of fruit increased gradually from 3rd to 13th trusses. The BER of fruit was not significantly influenced by CC compared to RC or PVC, but was sginificantly decreased by PVC compared to RC. Our results infer that CC was a potential substrate that could be widely used in tomato production. However, the inhibition of BER was still a challenge when CC was used as cultivation substrate for tomato.