Nader, Paris Island and Marul lettuce cultivars grown on polyethylene mulch and bare soils treated with either Nitrobein, Rhyzobactrein, or Hupotas. The objective of this study was to evaluate the responses of these cultivars to mulching and organic substance treatments. The obtained results revealed that lettuce grown on mulched soil significantly reduced IAA, GA3, ABA, CK, N, K, Ca, B, Na, and Fe in varying lettuce tissues. Owing to the increased root zone temperatures caused by polyethylene mulching in late summer. However, during ensuing winter mulched lettuce recovered and substantially improved yield, head fresh weight, TSS, Chlorophyll, seed yield and weight of 1000 seeds. Organic substances highly improved the growth performance of lettuce, particularly Rhyzobactrein, which sowed the best-performed yield and most other detected parameters. Nader was the most potent cultivar, where Paris Island and Marul failed to perform folded heads. Bitterness, Tip burns and Cu were not detected in all treatments and lettuce tissues. Dual and treble interaction treatments included in results and discussion sections