Lettuce has a lot of vitamin such as vitamin A, C, D, and B12 that is good for health. Also it needs an extra care to the plant, temperature, watering, and the needs of sunlight. The usage of fertilizers can help the plant to get the maximum productivity especially in flatland. This research aims to find out the efficiency of which fertilizer work the best for lettuce. This research was conducted in May-July 2020 and taken place at Kraton Village, Krian, Sidoarjo with the altitude ±10 masl and continued in agriculture laboratory of Faculty of Science and Technology, Muhammadiyah University. This research aims to find out which one is the best fertilizer for lettuce. The study design used Randomized Block Design (RBD) with 6 treatments and 3 replications. Based on this research, chemical fertilizer and animal's manure used for the growth of lettuce has significant effect on all variables observed, treatment using animal's manure is significally different from using chemical fertilizer except the cow's manure but the optimal productivity is using NPK that is included as chemical fertilizer with the dose of 1.2 grams/polybag is a treatment that gives plant a wet weight of 181.67 grams/plant.