This study aimed to evaluate the effects of organic growing media, NASA Liquid Organic Fertilizer (POC NASA) combined with AB Mix, and their interaction on the growth and yield of lettuce (Lactuca sativa L.) cultivated using a wick hydroponic system. The experiment was conducted from February to April 2026 at the Greenhouse and Production Laboratory, Department of Agroecotechnology, Faculty of Agriculture, Lambung Mangkurat University. A two-factor Completely Randomized Design (CRD) with three replications was employed. The first factor consisted of four growing media (rockwool, rice husk charcoal, cocopeat, and tree fern fiber), while the second factor comprised four nutrient combinations: 75% POC NASA + 25% AB Mix, 85% POC NASA + 15% AB Mix, 90% POC NASA + 10% AB Mix, and 100% POC NASA. The observed variables included plant height, leaf width, number of leaves, total fresh weight, and total dry weight. The results showed that the growing medium significantly affected all observed parameters. Rockwool produced the greatest plant height (22.42 cm) and leaf width (14.91 cm), whereas cocopeat resulted in the highest number of leaves (7.67 leaves), total fresh weight (122.72 g), and total dry weight (8.65 g). The nutrient factor significantly affected plant height and leaf width, with 75% POC NASA + 25% AB Mix producing the greatest plant height (16.74 cm) and 85% POC NASA + 15% AB Mix producing the widest leaves (14.69 cm). The interaction between growing media and nutrient combinations significantly affected only leaf width, with the combination of rockwool and 85% POC NASA + 15% AB Mix producing the widest leaves (16.02 cm). These findings indicate that selecting an appropriate growing medium combined with a balanced proportion of POC NASA and AB Mix can improve lettuce growth and productivity in a wick hydroponic system.